NM_177454.4:c.695A>C

Variant names:

• chr2-186747221-A-C
• rs961652693
• NM_177454.4:c.695A>C

Variant summary

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

The NM_177454.4(FAM171B):​c.695A>C​(p.His232Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,453,212 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. H232R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: FAM171B NM_177454.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62
• Publications: 0 publications found

Genes affected

FAM171B (HGNC:29412): (family with sequence similarity 171 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=0.26035297).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177454.4. 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
	FAM171B	NM_177454.4	MANE Select	c.695A>C	p.His232Pro	missense	Exon 4 of 8	NP_803237.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM171B	ENST00000304698.10	TSL:1 MANE Select	c.695A>C	p.His232Pro	missense	Exon 4 of 8	ENSP00000304108.5	Q6P995-1
	FAM171B	ENST00000909200.1		c.746A>C	p.His249Pro	missense	Exon 5 of 9	ENSP00000579259.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453212 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 722542

African (AFR) AF: 0.00 AC: 0 AN: 33126

American (AMR) AF: 0.00 AC: 0 AN: 42982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25898

East Asian (EAS) AF: 0.00 AC: 0 AN: 39348

South Asian (SAS) AF: 0.00 AC: 0 AN: 83726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53194

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109166

Other (OTH) AF: 0.00 AC: 0 AN: 60044

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.6
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.084
Sift	Benign	0.17	T
Sift4G	Benign	0.20	T
Polyphen		0.0	B
Vest4		0.36
MutPred		0.68		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.48
MPC		0.41
ClinPred		0.41	T
GERP RS		4.0
Varity_R		0.28
gMVP		0.86
Mutation Taster		=77/23	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: rs961652693; hg19: chr2-187611948;