chr1-16059922-T-C

Position:

• chr1-16059922-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_182623.3(FAM131C):​c.398A>G​(p.Asp133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D133A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.35

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2873702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131C	NM_182623.3	c.398A>G	p.Asp133Gly	missense_variant	5/7	ENST00000375662.5	NP_872429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM131C	ENST00000375662.5	c.398A>G	p.Asp133Gly	missense_variant	5/7	1	NM_182623.3	ENSP00000364814.4
FAM131C	ENST00000494078.1	n.472A>G		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1457402 Hom.: 0 Cov.: 52 AF XY: 0.00 AC XY: 0 AN XY: 725036

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: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.398A>G (p.D133G) alteration is located in exon 5 (coding exon 5) of the FAM131C gene. This alteration results from a A to G substitution at nucleotide position 398, causing the aspartic acid (D) at amino acid position 133 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.10
Sift	Benign	0.037	D
Sift4G	Benign	0.18	T
Polyphen		0.99	D
Vest4		0.44
MVP		0.40
MPC		1.4
ClinPred		0.56	D
GERP RS		3.6
Varity_R		0.15
gMVP		0.29

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: rs1189832298; hg19: chr1-16386417;