Variant 19-35753178-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019104.3(LIN37):c.369G>A(p.Met123Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000698 in 1,431,726 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

LIN37
NM_019104.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.00

Variant links:

Genes affected

LIN37 (HGNC:33234): (lin-37 DREAM MuvB core complex component) This gene encodes a protein expressed in the eye. [provided by RefSeq, Jul 2008]

LIN37 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LIN37	NM_019104.3 linkuse as main transcript	c.369G>A	p.Met123Ile	missense_variant	6/9	ENST00000301159.14	NP_061977.1
LIN37	NM_001369780.1 linkuse as main transcript	c.327G>A	p.Met109Ile	missense_variant	6/9		NP_001356709.1
LIN37	NR_163146.1 linkuse as main transcript	n.426+179G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN37	ENST00000301159.14 linkuse as main transcript	c.369G>A	p.Met123Ile	missense_variant	6/9	1	NM_019104.3	ENSP00000301159	P1
	ENST00000591091.1 linkuse as main transcript	n.238C>T		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000504

AC:

AN:

198602

Hom.:

AF XY:

0.00

AC XY:

AN XY:

106802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000345

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1431726

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2024

The c.369G>A (p.M123I) alteration is located in exon 6 (coding exon 6) of the LIN37 gene. This alteration results from a G to A substitution at nucleotide position 369, causing the methionine (M) at amino acid position 123 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-2.3

REVEL

Benign

0.27

Sift

Uncertain

0.0090

Sift4G

Benign

0.096

Polyphen

0.60

Vest4

0.78

MutPred

0.37

Gain of sheet (P = 0.0266);

MVP

0.46

MPC

0.33

ClinPred

0.85

GERP RS

4.9

Varity_R

0.54

gMVP

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over