X-34942922-G-A

Variant names:

• chrX-34942922-G-A
• rs756946994
• NM_152631.3:c.91G>A

Variant summary

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

The NM_152631.3(FAM47B):​c.91G>A​(p.Ala31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,098 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 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. A31S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
• Consequence: FAM47B NM_152631.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.703
• Publications: 1 publications found

Genes affected

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

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=0.084202826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152631.3. 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
	FAM47B	NM_152631.3	MANE Select	c.91G>A	p.Ala31Thr	missense	Exon 1 of 1	NP_689844.2	Q8NA70

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47B	ENST00000329357.6	TSL:6 MANE Select	c.91G>A	p.Ala31Thr	missense	Exon 1 of 1	ENSP00000328307.5	Q8NA70

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181805 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000727

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098098 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 1 AN XY: 363460

African (AFR) AF: 0.00 AC: 0 AN: 26392

American (AMR) AF: 0.00 AC: 0 AN: 35190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19384

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30200

South Asian (SAS) AF: 0.00 AC: 0 AN: 54129

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842054

Other (OTH) AF: 0.00 AC: 0 AN: 46091

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.91
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.084	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.70
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.041
Sift	Benign	0.37	T
Sift4G	Benign	0.20	T
Polyphen		0.91	P
Vest4		0.079
MutPred		0.24		Gain of phosphorylation at A31 (P = 0.0046)
MVP		0.47
MPC		0.19
ClinPred		0.20	T
GERP RS		-1.7
PromoterAI		0.0012	Neutral
Varity_R		0.12
gMVP		0.024
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: rs756946994; hg19: chrX-34961039; COSMIC: COSV107342241;