1-16058506-G-C

Position:

• chr1-16058506-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_182623.3(FAM131C):​c.774C>G​(p.His258Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000514 in 1,360,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 47)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.376

Genes affected

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

FAM131C (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06012234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131C	NM_182623.3	c.774C>G	p.His258Gln	missense_variant	7/7	ENST00000375662.5	NP_872429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM131C	ENST00000375662.5	c.774C>G	p.His258Gln	missense_variant	7/7	1	NM_182623.3	ENSP00000364814.4
FAM131C	ENST00000494078.1	n.848C>G		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes Cov.: 47

GnomAD4 exome AF: 0.00000514 AC: 7 AN: 1360782 Hom.: 0 Cov.: 74 AF XY: 0.00000598 AC XY: 4 AN XY: 668814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000562

Gnomad4 SAS exome AF: 0.0000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000376

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 47

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 14, 2023

The c.774C>G (p.H258Q) alteration is located in exon 7 (coding exon 7) of the FAM131C gene. This alteration results from a C to G substitution at nucleotide position 774, causing the histidine (H) at amino acid position 258 to be replaced by a glutamine (Q). 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	0.085
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.44
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.020
Sift	Benign	0.37	T
Sift4G	Benign	0.69	T
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.072		Gain of glycosylation at P260 (P = 0.1471);
MVP		0.15
MPC		0.43
ClinPred		0.022	T
GERP RS		-1.6
Varity_R		0.048
gMVP		0.094

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: rs867260430; hg19: chr1-16385001;