13-51251696-A-T

Variant names:

• chr13-51251696-A-T
• rs916964060
• NM_001242312.2:c.329A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001242312.2(FAM124A):​c.329A>T​(p.Glu110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,587,768 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: FAM124A NM_001242312.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23
• Publications: 0 publications found

Genes affected

FAM124A (HGNC:26413): (family with sequence similarity 124 member A)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26700228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM124A	NM_001242312.2	c.329A>T	p.Glu110Val	missense_variant	Exon 3 of 4	ENST00000322475.13	NP_001229241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM124A	ENST00000322475.13	c.329A>T	p.Glu110Val	missense_variant	Exon 3 of 4	1	NM_001242312.2	ENSP00000324625.8
FAM124A	ENST00000615498.4	c.329A>T	p.Glu110Val	missense_variant	Exon 3 of 3	1		ENSP00000481212.1
FAM124A	ENST00000280057.6	c.437A>T	p.Glu146Val	missense_variant	Exon 4 of 5	2		ENSP00000280057.6

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000100 AC: 2 AN: 199912 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000669

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000418 AC: 6 AN: 1435568 Hom.: 0 Cov.: 31 AF XY: 0.00000281 AC XY: 2 AN XY: 712310

African (AFR) AF: 0.00 AC: 0 AN: 32882

American (AMR) AF: 0.0000487 AC: 2 AN: 41072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.00 AC: 0 AN: 38284

South Asian (SAS) AF: 0.00 AC: 0 AN: 83444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00000364 AC: 4 AN: 1100196

Other (OTH) AF: 0.00 AC: 0 AN: 59476

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74354

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.437A>T (p.E146V) alteration is located in exon 4 (coding exon 4) of the FAM124A gene. This alteration results from a A to T substitution at nucleotide position 437, causing the glutamic acid (E) at amino acid position 146 to be replaced by a valine (V). 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	0.32
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	.;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.27	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.6	L;L;.
PhyloP100		3.2
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-4.3	.;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.018	.;D;D
Sift4G	Benign	0.096	T;T;T
Polyphen		0.59	P;D;D
Vest4		0.19
MutPred		0.30		Loss of solvent accessibility (P = 0.0089);Loss of solvent accessibility (P = 0.0089);.;
MVP		0.69
MPC		1.0
ClinPred		0.95	D
GERP RS		4.6
Varity_R		0.27
gMVP		0.67
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

dbSNP: rs916964060; hg19: chr13-51825832;