6-116762012-T-A

Variant names:

• chr6-116762012-T-A
• rs748216736
• NM_001085480.3:c.355A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001085480.3(FAM162B):​c.355A>T​(p.Ile119Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I119V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM162B NM_001085480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.355A>T	p.Ile119Phe	missense	Exon 3 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.355A>T	p.Ile119Phe	missense	Exon 3 of 4	ENSP00000357545.4	Q5T6X4
	FAM162B	ENST00000864732.1		c.388A>T	p.Ile130Phe	missense	Exon 3 of 4	ENSP00000534793.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451020 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 721270

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 85278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53108

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103808

Other (OTH) AF: 0.00 AC: 0 AN: 59814

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.019
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.93
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.091
Sift	Benign	0.076	T
Sift4G	Benign	0.086	T
Polyphen		0.96	D
Vest4		0.63
MutPred		0.51		Loss of MoRF binding (P = 0.1092)
MVP		0.29
MPC		1.6
ClinPred		0.74	D
GERP RS		2.1
Varity_R		0.19
gMVP		0.76
Mutation Taster		=79/21	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: rs748216736; hg19: chr6-117083175;