10-49131684-G-A

Variant names:

• chr10-49131684-G-A
• rs760185289
• NM_001164484.2:c.781C>T

Variant summary

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

The NM_001164484.2(FAM170B):​c.781C>T​(p.Pro261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,410 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P261T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FAM170B NM_001164484.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 0 publications found

Genes affected

FAM170B (HGNC:19736): (family with sequence similarity 170 member B) Predicted to be involved in fertilization; positive regulation of acrosome reaction; and regulation of fertilization. Located in acrosomal vesicle. [provided by Alliance of Genome Resources, Apr 2022]

FAM170B-AS1 (HGNC:45006): (FAM170B antisense RNA 1)

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=0.048826545).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164484.2. 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
	FAM170B	NM_001164484.2	MANE Select	c.781C>T	p.Pro261Ser	missense	Exon 2 of 2	NP_001157956.1	A6NMN3
	FAM170B-AS1	NR_038973.1		n.439-3972G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM170B	ENST00000311787.6	TSL:1 MANE Select	c.781C>T	p.Pro261Ser	missense	Exon 2 of 2	ENSP00000308292.6	A6NMN3
	FAM170B-AS1	ENST00000435809.2	TSL:3	n.424-4193G>A		intron	N/A
	FAM170B-AS1	ENST00000442525.5	TSL:2	n.439-3972G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399410 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690214

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078982

Other (OTH) AF: 0.00 AC: 0 AN: 58002

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.6
DANN	Benign	0.65
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.35
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.019
Sift	Benign	0.057	T
Sift4G	Benign	0.66	T
Polyphen		0.10	B
Vest4		0.087
MutPred		0.17		Gain of phosphorylation at P261 (P = 0.0081)
MVP		0.10
ClinPred		0.12	T
GERP RS		2.6
Varity_R		0.037
gMVP		0.11
Mutation Taster		=100/0	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: rs760185289; hg19: chr10-50339729; COSMIC: COSV104605662;