rs550385924

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 8P and 8B. PVS1BP6_Very_Strong

The NM_001433720.1(MLDHR):c.2T>C(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000104 in 383,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

MLDHR
NM_001433720.1 start_lost

Scores

Clinical Significance

Likely benign reviewed by expert panel U:1B:5

Conservation

PhyloP100: 4.25

Publications

2 publications found

Variant links:

Genes affected

MLDHR (HGNC:55481):

MLDHR links:

PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

PTEN links:

KLLN (HGNC:37212): (killin, p53 regulated DNA replication inhibitor) The protein encoded by this intronless gene is found in the nucleus, where it can inhibit DNA synthesis and promote S phase arrest coupled to apoptosis. The expression of this DNA binding protein is upregulated by transcription factor p53. [provided by RefSeq, Dec 2012]

KLLN Gene-Disease associations (from GenCC):

Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 4
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

KLLN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BP6

Variant 10-87863560-T-C is Benign according to our data. Variant chr10-87863560-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 127681.Status of the report is reviewed_by_expert_panel, 3 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001433720.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLDHR	NM_001433720.1		c.2T>C	p.Met1?	start_lost	Exon 1 of 1	NP_001420649.1	C0HLV8
PTEN	NM_000314.8	MANE Select	c.-910T>C		upstream_gene	N/A	NP_000305.3
KLLN	NM_001126049.2	MANE Select	c.-1073A>G		upstream_gene	N/A	NP_001119521.1	B2CW77

Ensembl Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MLDHR	ENST00000692337.1	c.2T>C	p.Met1?	start_lost	Exon 1 of 1	ENSP00000509326.1	C0HLV8
PTEN	ENST00000693560.1	c.-390T>C		5_prime_UTR	Exon 1 of 10	ENSP00000509861.1	A0A8I5KSF9
PTEN	ENST00000688308.1	c.-17+447T>C		intron	N/A	ENSP00000508752.1	P60484-1

Frequencies

GnomAD3 genomes

AF:

0.0000725

AC:

AN:

151628

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000984

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000125

AC:

AN:

231838

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

117842

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6532

American (AMR)

AF:

0.00

AC:

AN:

6876

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8514

East Asian (EAS)

AF:

0.000814

AC:

AN:

22106

South Asian (SAS)

AF:

0.00

AC:

AN:

2732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1226

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

148302

Other (OTH)

AF:

0.000723

AC:

AN:

15218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000725

AC:

AN:

151736

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41426

American (AMR)

AF:

0.0000655

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000987

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67862

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000155

Hom.:

Bravo

AF:

0.0000453

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Prostate cancer;C1854416:Macrocephaly-autism syndrome;C2751642:Glioma susceptibility 2;C3551915:Familial meningioma;CN072330:Cowden syndrome 1 (1)

PTEN hamartoma tumor syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

4.2

PromoterAI

0.59

Over-expression

(source)

Mutation Taster

=290/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over