X-149611399-T-A

Variant names:

• chrX-149611399-T-A
• rs782438408
• NM_032508.4:c.103A>T

Variant summary

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

The NM_032508.4(TMEM185A):​c.103A>T​(p.Ile35Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TMEM185A NM_032508.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43
• Publications: 0 publications found

Genes affected

TMEM185A (HGNC:17125): (transmembrane protein 185A) The protein encoded by this gene is predicted to be a transmembrane protein. This gene is best known for localizing to the CpG island of the fragile site FRAXF. The 5' untranslated region of this gene contains a CGG trinucleotide repeat sequence that normally consists of 7-40 tandem CGG repeats but which can expand to greater than 300 repeats. Methylation of the CpG island leads to transcriptional silencing of this gene, but neither the silencing nor an expanded repeat region appear to manifest itself in a clear phenotypic manner. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Aug 2013]

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=0.23991981).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032508.4. 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
	TMEM185A	NM_032508.4	MANE Select	c.103A>T	p.Ile35Phe	missense	Exon 2 of 7	NP_115897.1	Q8NFB2
	TMEM185A	NM_001282302.2		c.103A>T	p.Ile35Phe	missense	Exon 2 of 4	NP_001269231.1	E7EMM1
	TMEM185A	NM_001174092.3		c.39-2565A>T		intron	N/A	NP_001167563.1	B7Z4G6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM185A	ENST00000600449.8	TSL:1 MANE Select	c.103A>T	p.Ile35Phe	missense	Exon 2 of 7	ENSP00000471932.1	Q8NFB2
	TMEM185A	ENST00000507237.5	TSL:2	c.103A>T	p.Ile35Phe	missense	Exon 2 of 4	ENSP00000427766.1	E7EMM1
	TMEM185A	ENST00000611119.4	TSL:2	c.39-2565A>T		intron	N/A	ENSP00000483235.1	B7Z4G6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.085
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.73
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.4
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.082
Sift	Benign	0.56	T
Sift4G	Benign	0.54	T
Vest4		0.37
MutPred		0.40		Gain of methylation at R31 (P = 0.1116)
MVP		0.50
ClinPred		0.63	D
GERP RS		5.0
gMVP		0.71
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs782438408; hg19: chrX-148693082;