1-222750009-A-T

Variant names:

• chr1-222750009-A-T
• rs6683071
• NM_001394345.1:c.428A>T

Variant summary

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

The NM_001394345.1(FAM177B):​c.428A>T​(p.Gln143Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FAM177B NM_001394345.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 46 publications found

Genes affected

FAM177B (HGNC:34395): (family with sequence similarity 177 member B)

ENSG00000287684 (HGNC:):

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=0.04103613).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394345.1. 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
	FAM177B	NM_001394345.1	MANE Select	c.428A>T	p.Gln143Leu	missense	Exon 6 of 6	NP_001381274.1	A6PVY3-1
	FAM177B	NM_001324080.2		c.428A>T	p.Gln143Leu	missense	Exon 5 of 5	NP_001311009.1	A6PVY3-1
	FAM177B	NM_207468.3		c.428A>T	p.Gln143Leu	missense	Exon 6 of 6	NP_997351.2	A6PVY3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM177B	ENST00000445590.4	TSL:5 MANE Select	c.428A>T	p.Gln143Leu	missense	Exon 6 of 6	ENSP00000414451.2	A6PVY3-1
	FAM177B	ENST00000360827.6	TSL:5	c.428A>T	p.Gln143Leu	missense	Exon 6 of 6	ENSP00000354070.2	A6PVY3-1
	FAM177B	ENST00000893418.1		c.428A>T	p.Gln143Leu	missense	Exon 5 of 5	ENSP00000563477.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.016
DANN	Benign	0.58
DEOGEN2	Benign	0.028	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.10	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.4
PrimateAI	Benign	0.18	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.024
Sift	Benign	0.14	T
Sift4G	Benign	0.14	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.29		Loss of disorder (P = 0.0174)
MVP		0.014
MPC		0.16
ClinPred		0.12	T
GERP RS		-11
Varity_R		0.051
gMVP		0.093
Mutation Taster		=97/3	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: rs6683071; hg19: chr1-222923351;