3-184338389-T-A

Variant names:

• chr3-184338389-T-A
• NM_144635.5:c.91T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144635.5(FAM131A):​c.91T>A​(p.Ser31Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000777 in 1,287,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: FAM131A NM_144635.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.413

Genes affected

FAM131A (HGNC:28308): (family with sequence similarity 131 member A)

ACMG classification

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=0.17838821).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM131A	NM_144635.5	c.91T>A	p.Ser31Thr	missense_variant, splice_region_variant	Exon 2 of 6	ENST00000383847.7	NP_653236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM131A	ENST00000383847.7	c.91T>A	p.Ser31Thr	missense_variant, splice_region_variant	Exon 2 of 6	2	NM_144635.5	ENSP00000373360.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.77e-7 AC: 1 AN: 1287556 Hom.: 0 Cov.: 30 AF XY: 0.00000160 AC XY: 1 AN XY: 625688

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.69e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.91T>A (p.S31T) alteration is located in exon 2 (coding exon 2) of the FAM131A gene. This alteration results from a T to A substitution at nucleotide position 91, causing the serine (S) at amino acid position 31 to be replaced by a threonine (T). 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	0.088
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-0.0068
Eigen_PC	Benign	-0.036
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.36	.;N
REVEL	Benign	0.031
Sift	Benign	0.10	.;T
Sift4G	Benign	0.51	.;T
Vest4		0.20
MutPred		0.41		Loss of disorder (P = 0.0786);Loss of disorder (P = 0.0786);
MVP		0.53
MPC		0.36
ClinPred		0.074	T
GERP RS		1.1
Varity_R		0.054
gMVP		0.090

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-184056177;