Genetic Variant FAM162B:p.Arg10His (chr6-116765548-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001085480.3(FAM162B):c.29G>A(p.Arg10His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,384,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FAM162B
NM_001085480.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

FAM162B (HGNC:21549): (family with sequence similarity 162 member B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

FAM162B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07958683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM162B	NM_001085480.3 link	c.29G>A	p.Arg10His	missense_variant	Exon 1 of 4	ENST00000368557.6	NP_001078949.1	Q5T6X4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM162B	ENST00000368557.6 link	c.29G>A	p.Arg10His	missense_variant	Exon 1 of 4	1	NM_001085480.3	ENSP00000357545.4		Q5T6X4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1232194

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

594332

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:

0.0000119

Gnomad4 OTH exome

AF:

0.0000196

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.29G>A (p.R10H) alteration is located in exon 1 (coding exon 1) of the FAM162B gene. This alteration results from a G to A substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.56

M_CAP

Benign

0.016

MetaRNN

Benign

0.080

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.7

REVEL

Benign

0.067

Sift

Uncertain

0.010

Sift4G

Pathogenic

0.0

Polyphen

0.029

Vest4

0.11

MutPred

0.45

Loss of methylation at R10 (P = 0.0199);

MVP

0.11

MPC

0.53

ClinPred

0.26

GERP RS

1.4

Varity_R

0.094

gMVP

0.41

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over