chr3-184344672-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144635.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131A	NM_144635.5	MANE Select	c.803C>T	p.Pro268Leu	missense	Exon 6 of 6	NP_653236.3
	FAM131A	NM_001171093.2		c.548C>T	p.Pro183Leu	missense	Exon 6 of 6	NP_001164564.1	Q6UXB0-2
	FAM131A	NM_001366133.1		c.548C>T	p.Pro183Leu	missense	Exon 5 of 5	NP_001353062.1	Q6UXB0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131A	ENST00000383847.7	TSL:2 MANE Select	c.803C>T	p.Pro268Leu	missense	Exon 6 of 6	ENSP00000373360.2	Q6UXB0-3
	FAM131A	ENST00000340957.9	TSL:1	c.548C>T	p.Pro183Leu	missense	Exon 6 of 6	ENSP00000340974.5	Q6UXB0-2
	FAM131A	ENST00000855138.1		c.803C>T	p.Pro268Leu	missense	Exon 8 of 8	ENSP00000525197.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249288 AF XY: 0.00000741

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111750

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000374 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.2
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.064	T
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
Mutation Taster		=30/70	disease causing

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: rs753917077; hg19: chr3-184062460;