rs781054255

Variant names:

• chr1-16059890-G-T
• rs781054255
• NM_182623.3:c.430C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-16059890-G-T
• chr1-16059890-G-A
• chr1-16059890-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182623.3(FAM131C):​c.430C>A​(p.Arg144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,268,958 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 0.000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 3 publications found

Genes affected

FAM131C (HGNC:26717): (family with sequence similarity 131 member C)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0968512).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182623.3. 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
	FAM131C	NM_182623.3	MANE Select	c.430C>A	p.Arg144Ser	missense	Exon 5 of 7	NP_872429.2	Q96AQ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM131C	ENST00000375662.5	TSL:1 MANE Select	c.430C>A	p.Arg144Ser	missense	Exon 5 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.394C>A	p.Arg132Ser	missense	Exon 4 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.269-286C>A		intron	N/A	ENSP00000574434.1

Frequencies

GnomAD3 genomes AF: 0.0000729 AC: 3 AN: 41130 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00379

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000864

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247828 AF XY: 0.00

Gnomad AFR exome AF: 0.0000653

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000106 AC: 13 AN: 1227828 Hom.: 0 Cov.: 49 AF XY: 0.00000825 AC XY: 5 AN XY: 605742

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000326 AC: 1 AN: 30712

American (AMR) AF: 0.00 AC: 0 AN: 34302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.000139 AC: 2 AN: 14416

South Asian (SAS) AF: 0.0000154 AC: 1 AN: 64970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38764

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3454

European-Non Finnish (NFE) AF: 0.00000718 AC: 7 AN: 974864

Other (OTH) AF: 0.0000426 AC: 2 AN: 46960

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000140282), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000729 AC: 3 AN: 41130 Hom.: 0 Cov.: 0 AF XY: 0.0000502 AC XY: 1 AN XY: 19916

African (AFR) AF: 0.0000436 AC: 1 AN: 22920

American (AMR) AF: 0.00 AC: 0 AN: 2496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 614

East Asian (EAS) AF: 0.00379 AC: 1 AN: 264

South Asian (SAS) AF: 0.00 AC: 0 AN: 548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 64

European-Non Finnish (NFE) AF: 0.0000864 AC: 1 AN: 11574

Other (OTH) AF: 0.00 AC: 0 AN: 512

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Benign	0.37	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.089
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.23
MutPred		0.36		Loss of helix (P = 0.0376)
MVP		0.55
MPC		1.3
ClinPred		0.75	D
GERP RS		4.0
Varity_R		0.40
gMVP		0.40
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs781054255; hg19: chr1-16386385;