1-222750009-A-C

Position:

• chr1-222750009-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394345.1(FAM177B):​c.428A>C​(p.Gln143Pro) 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. 15/21 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. Q143R) has been classified as Likely benign.

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

Genes affected

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

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04217434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM177B	NM_001394345.1	c.428A>C	p.Gln143Pro	missense_variant	6/6	ENST00000445590.4	NP_001381274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM177B	ENST00000445590.4	c.428A>C	p.Gln143Pro	missense_variant	6/6	5	NM_001394345.1	ENSP00000414451	P1
	ENST00000654074.1	n.287-3113T>G		intron_variant, non_coding_transcript_variant
FAM177B	ENST00000360827.6	c.428A>C	p.Gln143Pro	missense_variant	6/6	5		ENSP00000354070	P1
FAM177B	ENST00000391880.6	c.*569A>C		3_prime_UTR_variant, NMD_transcript_variant	6/6	2		ENSP00000375752

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 48

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.048
DANN	Benign	0.67
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.12	.;T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.039
Sift	Benign	0.042	D;D
Sift4G	Uncertain	0.050	T;T
Polyphen		0.0	B;B
Vest4		0.11
MutPred		0.17		Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);
MVP		0.014
MPC		0.20
ClinPred		0.11	T
GERP RS		-11
Varity_R		0.093
gMVP		0.072

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

Publications

LitVar

Other links and lift over

dbSNP: rs6683071; hg19: chr1-222923351;