6-116765477-C-A

Variant names:

• chr6-116765477-C-A
• rs957087385
• NM_001085480.3:c.100G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001085480.3(FAM162B):​c.100G>T​(p.Ala34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,260,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A34T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: FAM162B NM_001085480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05188805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001085480.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM162B	NM_001085480.3	MANE Select	c.100G>T	p.Ala34Ser	missense	Exon 1 of 4	NP_001078949.1	Q5T6X4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM162B	ENST00000368557.6	TSL:1 MANE Select	c.100G>T	p.Ala34Ser	missense	Exon 1 of 4	ENSP00000357545.4	Q5T6X4
	FAM162B	ENST00000864732.1		c.100G>T	p.Ala34Ser	missense	Exon 1 of 4	ENSP00000534793.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1260492 Hom.: 0 Cov.: 31 AF XY: 0.00000164 AC XY: 1 AN XY: 609426

African (AFR) AF: 0.00 AC: 0 AN: 25240

American (AMR) AF: 0.00 AC: 0 AN: 16204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17798

East Asian (EAS) AF: 0.00 AC: 0 AN: 31164

South Asian (SAS) AF: 0.00 AC: 0 AN: 59436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3552

European-Non Finnish (NFE) AF: 9.81e-7 AC: 1 AN: 1019636

Other (OTH) AF: 0.00 AC: 0 AN: 52080

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.58
DANN	Benign	0.39
DEOGEN2	Benign	0.00067	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.48
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.038
Sift	Benign	0.55	T
Sift4G	Benign	0.69	T
Polyphen		0.0050	B
Vest4		0.044
MutPred		0.29		Gain of glycosylation at A34 (P = 0.0075)
MVP		0.067
MPC		0.39
ClinPred		0.035	T
GERP RS		0.062
PromoterAI		-0.031	Neutral
Varity_R		0.057
gMVP		0.24
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs957087385; hg19: chr6-117086640;