10-49132173-C-T

Variant names:

• chr10-49132173-C-T
• rs911020722
• NM_001164484.2:c.292G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164484.2(FAM170B):​c.292G>A​(p.Glu98Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,399,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000031 (0 hom.)
• Consequence: FAM170B NM_001164484.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.606

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09337965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM170B	NM_001164484.2	c.292G>A	p.Glu98Lys	missense_variant	Exon 2 of 2	ENST00000311787.6	NP_001157956.1
FAM170B-AS1	NR_038973.1	n.439-3483C>T		intron_variant	Intron 1 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM170B	ENST00000311787.6	c.292G>A	p.Glu98Lys	missense_variant	Exon 2 of 2	1	NM_001164484.2	ENSP00000308292.6
FAM170B-AS1	ENST00000435809.1	n.192-3704C>T		intron_variant	Intron 1 of 2	3
FAM170B-AS1	ENST00000442525.5	n.439-3483C>T		intron_variant	Intron 1 of 5	2
FAM170B-AS1	ENST00000443389.5	n.434-9080C>T		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000642 AC: 1 AN: 155696 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000307 AC: 43 AN: 1399450 Hom.: 0 Cov.: 39 AF XY: 0.0000319 AC XY: 22 AN XY: 690236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000389

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.292G>A (p.E98K) alteration is located in exon 2 (coding exon 2) of the FAM170B gene. This alteration results from a G to A substitution at nucleotide position 292, causing the glutamic acid (E) at amino acid position 98 to be replaced by a lysine (K). 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	0.073
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.045
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		0.39	B
Vest4		0.16
MutPred		0.40		Gain of ubiquitination at E98 (P = 0.0109);
MVP		0.040
ClinPred		0.073	T
GERP RS		1.1
Varity_R		0.043
gMVP		0.089

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

LitVar

Other links and lift over

dbSNP: rs911020722; hg19: chr10-50340218;