rs1558249475

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-222746624-C-A
• chr1-222746624-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394345.1(FAM177B):​c.79C>A​(p.His27Asn) 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. 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. H27Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM177B NM_001394345.1 missense
• Clinical Significance: Not reported in ClinVar
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32775635).

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>A	p.His27Asn	missense	Exon 3 of 6	NP_001381274.1	A6PVY3-1
	FAM177B	NM_001324080.2		c.79C>A	p.His27Asn	missense	Exon 2 of 5	NP_001311009.1	A6PVY3-1
	FAM177B	NM_207468.3		c.79C>A	p.His27Asn	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>A	p.His27Asn	missense	Exon 3 of 6	ENSP00000414451.2	A6PVY3-1
	FAM177B	ENST00000360827.6	TSL:5	c.79C>A	p.His27Asn	missense	Exon 3 of 6	ENSP00000354070.2	A6PVY3-1
	FAM177B	ENST00000893418.1		c.79C>A	p.His27Asn	missense	Exon 2 of 5	ENSP00000563477.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.037
Eigen_PC	Benign	-0.055
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.36
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Benign	0.11
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.016	D
Polyphen		0.97	D
Vest4		0.43
MutPred		0.48		Gain of relative solvent accessibility (P = 0.09)
MVP		0.072
MPC		0.63
ClinPred		0.84	D
GERP RS		2.8
Varity_R		0.76
gMVP		0.36
Mutation Taster		=86/14	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: rs1558249475; hg19: chr1-222919966;