X-34130094-C-T

Variant names:

• chrX-34130094-C-T
• rs1922404143
• NM_203408.4:c.2185G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_203408.4(FAM47A):​c.2185G>A​(p.Val729Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,097,059 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: FAM47A NM_203408.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.275
• Publications: 0 publications found

Genes affected

FAM47A (HGNC:29962): (family with sequence similarity 47 member A)

ENSG00000233928 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024528742).
• BP6: Variant X-34130094-C-T is Benign according to our data. Variant chrX-34130094-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3847730.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203408.4. 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
	FAM47A	NM_203408.4	MANE Select	c.2185G>A	p.Val729Ile	missense	Exon 1 of 1	NP_981953.2	Q5JRC9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM47A	ENST00000346193.5	TSL:6 MANE Select	c.2185G>A	p.Val729Ile	missense	Exon 1 of 1	ENSP00000345029.3	Q5JRC9
	ENSG00000233928	ENST00000653446.1		n.390+53525C>T		intron	N/A
	ENSG00000233928	ENST00000656777.1		n.452+53525C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1097059 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362469

African (AFR) AF: 0.00 AC: 0 AN: 26354

American (AMR) AF: 0.00 AC: 0 AN: 34991

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19308

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 53875

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4122

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841669

Other (OTH) AF: 0.00 AC: 0 AN: 46025

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.088
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.043
DANN	Benign	0.14
DEOGEN2	Benign	0.0027	T
FATHMM_MKL	Benign	0.00010	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.8	N
PhyloP100		-0.28
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.53	N
REVEL	Benign	0.035
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.18	B
Vest4		0.052
MutPred		0.15		Gain of disorder (P = 0.147)
MVP		0.068
MPC		0.19
ClinPred		0.038	T
GERP RS		-2.3
Varity_R		0.022
gMVP		0.013
Mutation Taster		=99/1	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: rs1922404143; hg19: chrX-34148211; COSMIC: COSV60494022;