chr1-222746624-C-T

Variant names:

• chr1-222746624-C-T
• rs1558249475
• NM_001394345.1:c.79C>T

Variant summary

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

The NM_001394345.1(FAM177B):​c.79C>T​(p.His27Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,100 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: FAM177B NM_001394345.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.358
• Publications: 0 publications found

Genes affected

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

ENSG00000287684 (HGNC:):

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=0.16010895).

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.79C>T	p.His27Tyr	missense	Exon 3 of 6	NP_001381274.1	A6PVY3-1
	FAM177B	NM_001324080.2		c.79C>T	p.His27Tyr	missense	Exon 2 of 5	NP_001311009.1	A6PVY3-1
	FAM177B	NM_207468.3		c.79C>T	p.His27Tyr	missense	Exon 3 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.79C>T	p.His27Tyr	missense	Exon 3 of 6	ENSP00000414451.2	A6PVY3-1
	FAM177B	ENST00000360827.6	TSL:5	c.79C>T	p.His27Tyr	missense	Exon 3 of 6	ENSP00000354070.2	A6PVY3-1
	FAM177B	ENST00000893418.1		c.79C>T	p.His27Tyr	missense	Exon 2 of 5	ENSP00000563477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460100 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726558

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110402

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.36
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.039
Sift	Benign	0.074	T
Sift4G	Benign	0.32	T
Polyphen		0.015	B
Vest4		0.16
MutPred		0.44		Gain of sheet (P = 0.0477)
MVP		0.014
MPC		0.20
ClinPred		0.11	T
GERP RS		2.8
Varity_R		0.21
gMVP		0.41
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1558249475; hg19: chr1-222919966;