Variant chr1-16058705-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_182623.3(FAM131C):c.575T>C(p.Ile192Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 35)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FAM131C
NM_182623.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0200

Variant links:

Genes affected

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

FAM131C links:

FAM131C (HGNC:):

FAM131C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043076724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM131C	NM_182623.3 linkuse as main transcript	c.575T>C	p.Ile192Thr	missense_variant	7/7	ENST00000375662.5	NP_872429.2	Q96AQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM131C	ENST00000375662.5 linkuse as main transcript	c.575T>C	p.Ile192Thr	missense_variant	7/7	1	NM_182623.3	ENSP00000364814.4		Q96AQ9
FAM131C	ENST00000494078.1 linkuse as main transcript	n.649T>C		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151420

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000208

AC:

AN:

1441898

Hom.:

Cov.:

AF XY:

0.00000420

AC XY:

AN XY:

715012

show subpopulations

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:

0.00000272

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151538

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74038

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000845

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2024

The c.575T>C (p.I192T) alteration is located in exon 7 (coding exon 7) of the FAM131C gene. This alteration results from a T to C substitution at nucleotide position 575, causing the isoleucine (I) at amino acid position 192 to be replaced by a threonine (T). 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

0.19

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.014

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.66

M_CAP

Benign

0.0070

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.82

REVEL

Benign

0.035

Sift

Uncertain

0.010

Sift4G

Benign

0.44

Polyphen

0.020

Vest4

0.049

MutPred

0.22

Loss of stability (P = 0.0023);

MVP

0.095

MPC

0.58

ClinPred

0.15

GERP RS

0.28

Varity_R

0.078

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over