chr10-49131878-C-G

Variant names:

• chr10-49131878-C-G
• NM_001164484.2:c.587G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001164484.2(FAM170B):​c.587G>C​(p.Trp196Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FAM170B NM_001164484.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.66

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM170B	NM_001164484.2	c.587G>C	p.Trp196Ser	missense_variant	Exon 2 of 2	ENST00000311787.6	NP_001157956.1
FAM170B-AS1	NR_038973.1	n.439-3778C>G		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM170B	ENST00000311787.6	c.587G>C	p.Trp196Ser	missense_variant	Exon 2 of 2	1	NM_001164484.2	ENSP00000308292.6
FAM170B-AS1	ENST00000435809.1	n.192-3999C>G		intron_variant	Intron 1 of 2	3
FAM170B-AS1	ENST00000442525.5	n.439-3778C>G		intron_variant	Intron 1 of 5	2
FAM170B-AS1	ENST00000443389.5	n.434-9375C>G		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.587G>C (p.W196S) alteration is located in exon 2 (coding exon 2) of the FAM170B gene. This alteration results from a G to C substitution at nucleotide position 587, causing the tryptophan (W) at amino acid position 196 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Benign	0.89
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.041
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-12	D
REVEL	Benign	0.28
Sift	Benign	0.14	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.38
MutPred		0.77		Gain of disorder (P = 0.0017);
MVP		0.32
ClinPred		0.85	D
GERP RS		3.8
Varity_R		0.25
gMVP		0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-50339923;