NM_182623.3:c.400G>A

Variant names:

• chr1-16059920-C-T
• rs561644267
• NM_182623.3:c.400G>A

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.400G>A​(p.Glu134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,566 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 0.000014 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11
• Publications: 0 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=0.13927537).

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.400G>A	p.Glu134Lys	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.400G>A	p.Glu134Lys	missense	Exon 5 of 7	ENSP00000364814.4	Q96AQ9
	FAM131C	ENST00000943020.1		c.364G>A	p.Glu122Lys	missense	Exon 4 of 6	ENSP00000613079.1
	FAM131C	ENST00000904375.1		c.269-316G>A		intron	N/A	ENSP00000574434.1

Frequencies

GnomAD3 genomes AF: 0.0000141 AC: 1 AN: 71074 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000182

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000810 AC: 2 AN: 246972 AF XY: 0.00000743

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000721 AC: 10 AN: 1387382 Hom.: 0 Cov.: 48 AF XY: 0.00000870 AC XY: 6 AN XY: 689324

African (AFR) AF: 0.00 AC: 0 AN: 32556

American (AMR) AF: 0.00 AC: 0 AN: 40454

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24004

East Asian (EAS) AF: 0.00 AC: 0 AN: 29684

South Asian (SAS) AF: 0.00 AC: 0 AN: 81352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4182

European-Non Finnish (NFE) AF: 0.00000935 AC: 10 AN: 1069702

Other (OTH) AF: 0.00 AC: 0 AN: 55998

GnomAD4 genome AF: 0.0000140 AC: 1 AN: 71184 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 34536

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

African (AFR) AF: 0.00 AC: 0 AN: 29588

American (AMR) AF: 0.000182 AC: 1 AN: 5500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1360

East Asian (EAS) AF: 0.00 AC: 0 AN: 1238

South Asian (SAS) AF: 0.00 AC: 0 AN: 1520

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26462

Other (OTH) AF: 0.00 AC: 0 AN: 950

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.028	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.36		Gain of ubiquitination at E134 (P = 0.0082)
MVP		0.31
MPC		1.3
ClinPred		0.94	D
GERP RS		4.7
Varity_R		0.21
gMVP		0.34
Mutation Taster		=88/12	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: rs561644267; hg19: chr1-16386415;