chr1-16058535-C-T

Variant names:

• chr1-16058535-C-T
• rs767898181
• NM_182623.3:c.745G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182623.3(FAM131C):​c.745G>A​(p.Gly249Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,523,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 48)
  • Exomes 𝑓: 0.000041 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.621
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029033273).

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.745G>A	p.Gly249Arg	missense	Exon 7 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.745G>A	p.Gly249Arg	missense	Exon 7 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.709G>A	p.Gly237Arg	missense	Exon 6 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.562G>A	p.Gly188Arg	missense	Exon 6 of 6	ENSP00000574434.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152232 Hom.: 0 Cov.: 48

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000696 AC: 8 AN: 114868 AF XY: 0.0000497

Gnomad AFR exome AF: 0.000150

Gnomad AMR exome AF: 0.000110

Gnomad ASJ exome AF: 0.000798

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000234

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000408 AC: 56 AN: 1371610 Hom.: 0 Cov.: 83 AF XY: 0.0000415 AC XY: 28 AN XY: 675080

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

African (AFR) AF: 0.000128 AC: 4 AN: 31212

American (AMR) AF: 0.0000648 AC: 2 AN: 30862

Ashkenazi Jewish (ASJ) AF: 0.000697 AC: 16 AN: 22950

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35692

South Asian (SAS) AF: 0.00 AC: 0 AN: 74774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47126

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3942

European-Non Finnish (NFE) AF: 0.0000290 AC: 31 AN: 1068292

Other (OTH) AF: 0.0000352 AC: 2 AN: 56760

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152232 Hom.: 0 Cov.: 48 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

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

African (AFR) AF: 0.000145 AC: 6 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68024

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000227263), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000192 Hom.: 0

ExAC AF: 0.0000144 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	0.091
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.62
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.030
Sift	Benign	0.051	T
Sift4G	Benign	0.17	T
Polyphen		0.23	B
Vest4		0.065
MutPred		0.14		Gain of solvent accessibility (P = 0.019)
MVP		0.36
MPC		0.65
ClinPred		0.027	T
GERP RS		0.38
Varity_R		0.049
gMVP		0.20
Mutation Taster		=99/1	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: rs767898181; hg19: chr1-16385030;