rs1283517642

Variant names:

• chr10-49131905-A-C
• rs1283517642
• NM_001164484.2:c.560T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-49131905-A-C
• chr10-49131905-A-G

Variant summary

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

The NM_001164484.2(FAM170B):​c.560T>G​(p.Leu187Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000788 in 1,395,560 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000079 (0 hom.)
• Consequence: FAM170B NM_001164484.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.214
• 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: 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=0.09048897).

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.560T>G	p.Leu187Arg	missense	Exon 2 of 2	NP_001157956.1	A6NMN3
	FAM170B-AS1	NR_038973.1		n.439-3751A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM170B	ENST00000311787.6	TSL:1 MANE Select	c.560T>G	p.Leu187Arg	missense	Exon 2 of 2	ENSP00000308292.6	A6NMN3
	FAM170B-AS1	ENST00000435809.2	TSL:3	n.424-3972A>C		intron	N/A
	FAM170B-AS1	ENST00000442525.5	TSL:2	n.439-3751A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000788 AC: 11 AN: 1395560 Hom.: 0 Cov.: 85 AF XY: 0.0000116 AC XY: 8 AN XY: 688470

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35696

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: 79230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45662

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000927 AC: 10 AN: 1078788

Other (OTH) AF: 0.0000172 AC: 1 AN: 57972

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.13
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.21
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.62	N
REVEL	Benign	0.060
Sift	Benign	0.56	T
Sift4G	Benign	0.073	T
Polyphen		0.74	P
Vest4		0.26
MutPred		0.32		Gain of solvent accessibility (P = 0.0171)
MVP		0.42
ClinPred		0.18	T
GERP RS		1.1
Varity_R		0.049
gMVP		0.16
Mutation Taster		=93/7	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: rs1283517642; hg19: chr10-50339950;