6-116765543-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001085480.3(FAM162B):c.34G>A(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000809 in 1,236,508 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: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: FAM162B NM_001085480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.468

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]

ACMG classification

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=0.07753363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM162B	NM_001085480.3	c.34G>A	p.Gly12Ser	missense_variant	1/4	ENST00000368557.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM162B	ENST00000368557.6	c.34G>A	p.Gly12Ser	missense_variant	1/4	1	NM_001085480.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.09e-7 AC: 1 AN: 1236508 Hom.: 0 Cov.: 31 AF XY: 0.00000168 AC XY: 1 AN XY: 596784

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: 9.88e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Mar 17, 2023

The c.34G>A (p.G12S) 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 34, causing the glycine (G) at amino acid position 12 to be replaced by a serine (S). 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	0.20
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.0
Dann	Benign	0.93
DEOGEN2	Benign	0.00095	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.52	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	0.71	T
Polyphen		0.64	P
Vest4		0.12
MutPred		0.46		Gain of phosphorylation at G12 (P = 0.0295);
MVP		0.10
MPC		0.92
ClinPred		0.31	T
GERP RS		0.26
Varity_R		0.032
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: rs1268134068; hg19: chr6-117086706;