chr1-16059916-T-C

Position:

• chr1-16059916-T-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.404A>G​(p.His135Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,363,348 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: 19)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: FAM131C NM_182623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160

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=0.038629085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131C	NM_182623.3	c.404A>G	p.His135Arg	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.404A>G	p.His135Arg	missense_variant	5/7	1	NM_182623.3	ENSP00000364814.4
FAM131C	ENST00000494078.1	n.478A>G		non_coding_transcript_exon_variant	4/6	3

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD3 exomes AF: 0.00000809 AC: 2 AN: 247218 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134734

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 14 AN: 1363348 Hom.: 0 Cov.: 49 AF XY: 0.0000133 AC XY: 9 AN XY: 676998

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: 0.0000133

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 19

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000118 AC: 1

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

Jun 10, 2024

The c.404A>G (p.H135R) 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 404, causing the histidine (H) at amino acid position 135 to be replaced by an arginine (R). 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	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.0
DANN	Benign	0.96
DEOGEN2	Benign	0.0038	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.026
Sift	Benign	0.24	T
Sift4G	Benign	0.57	T
Polyphen		0.0030	B
Vest4		0.11
MVP		0.20
MPC		0.54
ClinPred		0.068	T
GERP RS		2.2
Varity_R		0.056
gMVP		0.32

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: rs377599440; hg19: chr1-16386411;