chr6-116765489-G-A

Variant names:

• chr6-116765489-G-A
• rs762164285
• NM_001085480.3:c.88C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001085480.3(FAM162B):​c.88C>T​(p.Arg30Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000803 in 1,407,742 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000088 (0 hom.)
• Consequence: FAM162B NM_001085480.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.137
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059510887).

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.88C>T	p.Arg30Trp	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.88C>T	p.Arg30Trp	missense	Exon 1 of 4	ENSP00000357545.4	Q5T6X4
	FAM162B	ENST00000864732.1		c.88C>T	p.Arg30Trp	missense	Exon 1 of 4	ENSP00000534793.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000579 AC: 2 AN: 34550 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000884 AC: 111 AN: 1255576 Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 49 AN XY: 606992

African (AFR) AF: 0.0000401 AC: 1 AN: 24944

American (AMR) AF: 0.000442 AC: 7 AN: 15848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17710

East Asian (EAS) AF: 0.00 AC: 0 AN: 30780

South Asian (SAS) AF: 0.00 AC: 0 AN: 58720

European-Finnish (FIN) AF: 0.0000296 AC: 1 AN: 33818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3534

European-Non Finnish (NFE) AF: 0.0000982 AC: 100 AN: 1018270

Other (OTH) AF: 0.0000385 AC: 2 AN: 51952

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.0000214 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.9
DANN	Benign	0.91
DEOGEN2	Benign	0.0015	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.14
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.018
Sift	Benign	0.14	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.51		Loss of methylation at R30 (P = 0.0179)
MVP		0.040
MPC		0.44
ClinPred		0.034	T
GERP RS		-3.0
PromoterAI		0.028	Neutral
Varity_R		0.033
gMVP		0.31
Mutation Taster		=99/1	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: rs762164285; hg19: chr6-117086652; COSMIC: COSV100882781;