6-116765519-C-A

Variant names:

• chr6-116765519-C-A
• rs755407736
• NM_001085480.3:c.58G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001085480.3(FAM162B):​c.58G>T​(p.Gly20Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000804 in 1,243,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G20R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: FAM162B NM_001085480.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10832998).

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.58G>T	p.Gly20Cys	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.58G>T	p.Gly20Cys	missense	Exon 1 of 4	ENSP00000357545.4	Q5T6X4
	FAM162B	ENST00000864732.1		c.58G>T	p.Gly20Cys	missense	Exon 1 of 4	ENSP00000534793.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.04e-7 AC: 1 AN: 1243452 Hom.: 0 Cov.: 31 AF XY: 0.00000167 AC XY: 1 AN XY: 600544

African (AFR) AF: 0.00 AC: 0 AN: 24340

American (AMR) AF: 0.00 AC: 0 AN: 15084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17530

East Asian (EAS) AF: 0.00 AC: 0 AN: 29810

South Asian (SAS) AF: 0.0000178 AC: 1 AN: 56290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3464

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014616

Other (OTH) AF: 0.00 AC: 0 AN: 51580

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.15
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.092
Sift	Benign	0.032	D
Sift4G	Uncertain	0.011	D
Polyphen		0.69	P
Vest4		0.15
MutPred		0.59		Gain of sheet (P = 0.0344)
MVP		0.055
MPC		1.1
ClinPred		0.31	T
GERP RS		-2.4
PromoterAI		-0.053	Neutral
Varity_R		0.14
gMVP		0.37
Mutation Taster		=96/4	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: rs755407736; hg19: chr6-117086682;