Variant 4-186154634-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001395294.1(FAM149A):c.1252G>C(p.Glu418Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,460,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

FAM149A
NM_001395294.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.69

Variant links:

Genes affected

FAM149A (HGNC:24527): (family with sequence similarity 149 member A)

FAM149A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08900902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM149A	NM_001395294.1 linkuse as main transcript	c.1252G>C	p.Glu418Gln	missense_variant	6/14	ENST00000706927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM149A	ENST00000706927.1 linkuse as main transcript	c.1252G>C	p.Glu418Gln	missense_variant	6/14		NM_001395294.1	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250834

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1460822

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

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

Dec 01, 2022

The c.379G>C (p.E127Q) alteration is located in exon 6 (coding exon 3) of the FAM149A gene. This alteration results from a G to C substitution at nucleotide position 379, causing the glutamic acid (E) at amino acid position 127 to be replaced by a glutamine (Q). 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

Benign

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.026

.;T;.;.;.;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.76

.;T;.;.;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.089

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;L;.;.;.;.

MutationTaster

Benign

0.77

D;N;N;N;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.33

T;T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T;T

Polyphen

0.70

.;P;.;.;.;.

Vest4

0.21

MutPred

0.24

.;Loss of solvent accessibility (P = 0.0174);.;.;.;.;

MVP

0.085

MPC

0.14

ClinPred

0.14

GERP RS

2.6

Varity_R

0.072

gMVP

0.25

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

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