X-103964564-C-G

Variant names:

• chrX-103964564-C-G
• rs368916522
• NM_194324.4:c.42C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_194324.4(TMSB15B):​c.42C>G​(p.Asp14Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: TMSB15B NM_194324.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

Genes affected

TMSB15B (HGNC:28612): (thymosin beta 15B) Predicted to enable actin monomer binding activity. Involved in positive regulation of cell migration. Predicted to be located in cytoskeleton. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18510363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMSB15B	NM_194324.4	c.42C>G	p.Asp14Glu	missense_variant	Exon 2 of 3	ENST00000540220.6	NP_919305.2
TMSB15B	NM_001350213.2	c.42C>G	p.Asp14Glu	missense_variant	Exon 3 of 4		NP_001337142.1
TMSB15B	NM_001350211.2	c.42C>G	p.Asp14Glu	missense_variant	Exon 3 of 4		NP_001337140.1
TMSB15B	NM_001350212.2	c.42C>G	p.Asp14Glu	missense_variant	Exon 3 of 4		NP_001337141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMSB15B	ENST00000540220.6	c.42C>G	p.Asp14Glu	missense_variant	Exon 2 of 3	1	NM_194324.4	ENSP00000455371.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000109 AC: 2 AN: 182863 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67479

Gnomad AFR exome AF: 0.000153

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ESP6500AA AF: 0.000381 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.42C>G (p.D14E) alteration is located in exon 2 (coding exon 1) of the TMSB15B gene. This alteration results from a C to G substitution at nucleotide position 42, causing the aspartic acid (D) at amino acid position 14 to be replaced by a glutamic acid (E). 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
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T;.;T;T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.87	.;.;D;.;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T;T;T;T
PROVEAN	Uncertain	-3.2	D;D;D;D;D
Sift	Benign	0.034	D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D
Vest4		0.40
MVP		0.51
MPC		0.23
GERP RS		2.9
Varity_R		0.31
gMVP		0.0034

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: rs368916522; hg19: chrX-103219137;