Genetic Variant HHIPL1:p.Pro21Ser (chr14-99645268-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001127258.3(HHIPL1):c.61C>T(p.Pro21Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HHIPL1
NM_001127258.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.54

Publications

0 publications found

Variant links:

Genes affected

HHIPL1 (HGNC:19710): (HHIP like 1) This gene encodes a protein that belongs to the glucose/sorbosone dehydrogenase family. The encoded protein also contains a domain that binds folate and reduced folic acid derivatives. [provided by RefSeq, Jul 2016]

HHIPL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.801

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127258.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HHIPL1	NM_001127258.3	MANE Select	c.61C>T	p.Pro21Ser	missense	Exon 1 of 9	NP_001120730.1	F1T0G3
HHIPL1	NM_032425.5		c.61C>T	p.Pro21Ser	missense	Exon 1 of 8	NP_115801.3	Q96JK4-2
HHIPL1	NM_001329411.2		c.61-6956C>T		intron	N/A	NP_001316340.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HHIPL1	ENST00000330710.10	TSL:1 MANE Select	c.61C>T	p.Pro21Ser	missense	Exon 1 of 9	ENSP00000330601.5	Q96JK4-1
HHIPL1	ENST00000357223.2	TSL:1	c.61C>T	p.Pro21Ser	missense	Exon 1 of 8	ENSP00000349757.2	Q96JK4-2
HHIPL1	ENST00000949017.1		c.61C>T	p.Pro21Ser	missense	Exon 1 of 9	ENSP00000619076.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1266968

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

622048

African (AFR)

AF:

0.00

AC:

AN:

25482

American (AMR)

AF:

0.00

AC:

AN:

19728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21036

East Asian (EAS)

AF:

0.00

AC:

AN:

27366

South Asian (SAS)

AF:

0.00

AC:

AN:

63624

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3666

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1021702

Other (OTH)

AF:

0.00

AC:

AN:

51910

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

0.0063

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.47

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.31

MutationAssessor

Pathogenic

3.0

PhyloP100

6.5

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.36

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.74

MutPred

0.62

Gain of helix (P = 0.062)

MVP

0.53

MPC

1.2

ClinPred

1.0

GERP RS

3.7

PromoterAI

0.49

Neutral

(source)

Varity_R

0.46

gMVP

0.61

Mutation Taster

=51/49

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over