X-34942944-T-C

Variant names:

• chrX-34942944-T-C
• rs1250962939
• NM_152631.3:c.113T>C

Variant summary

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

The NM_152631.3(FAM47B):​c.113T>C​(p.Leu38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,179 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts 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: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: FAM47B NM_152631.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.232

Genes affected

FAM47B (HGNC:26659): (family with sequence similarity 47 member B)

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=0.16288406).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM47B	NM_152631.3	c.113T>C	p.Leu38Pro	missense_variant	Exon 1 of 1	ENST00000329357.6	NP_689844.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM47B	ENST00000329357.6	c.113T>C	p.Leu38Pro	missense_variant	Exon 1 of 1	6	NM_152631.3	ENSP00000328307.5

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.00000549 AC: 1 AN: 182230 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66800

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000366

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098179 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363533

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.0000284

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.113T>C (p.L38P) alteration is located in exon 1 (coding exon 1) of the FAM47B gene. This alteration results from a T to C substitution at nucleotide position 113, causing the leucine (L) at amino acid position 38 to be replaced by a proline (P). 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	0.18
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.025	T
FATHMM_MKL	Benign	0.0029	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.044
Sift	Benign	0.044	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.78	P
Vest4		0.24
MutPred		0.45		Gain of disorder (P = 0.0063);
MVP		0.13
MPC		0.98
ClinPred		0.79	D
GERP RS		-0.44
Varity_R		0.50
gMVP		0.044

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: rs1250962939; hg19: chrX-34961061;