3-184344672-C-T

Variant names:

• chr3-184344672-C-T
• rs753917077
• NM_144635.5:c.803C>T

Variant summary

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

The NM_144635.5(FAM131A):​c.803C>T​(p.Pro268Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,046 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: 0.0000027 (0 hom.)
• Consequence: FAM131A NM_144635.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

Genes affected

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

ACMG classification

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 rank	MANE	Protein	UniProt
FAM131A	NM_144635.5	c.803C>T	p.Pro268Leu	missense_variant	Exon 6 of 6	ENST00000383847.7	NP_653236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM131A	ENST00000383847.7	c.803C>T	p.Pro268Leu	missense_variant	Exon 6 of 6	2	NM_144635.5	ENSP00000373360.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249288 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135002

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: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460046 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726424

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: 0.0000192

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000374 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.803C>T (p.P268L) alteration is located in exon 6 (coding exon 6) of the FAM131A gene. This alteration results from a C to T substitution at nucleotide position 803, causing the proline (P) at amino acid position 268 to be replaced by a leucine (L). 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	0.26
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	.;D;.;D;D;D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	.;.;.;.;.;.;.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.2	D;D;D;D;.;D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D;D;D;D;.;D;D;D
Sift4G	Benign	0.064	T;D;T;T;.;D;T;D
Polyphen		1.0	.;D;.;.;.;.;.;.
Vest4		0.85
MutPred		0.34		.;.;.;.;.;.;.;Loss of helix (P = 0.0376);
MVP		0.68
MPC		1.2
ClinPred		0.96	D
GERP RS		5.4
Varity_R		0.18
gMVP		0.68

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

Other links and lift over

dbSNP: rs753917077; hg19: chr3-184062460;