X-135098412-T-C

Variant names:

• chrX-135098412-T-C
• rs782529285
• NM_001348255.2:c.222A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001348255.2(SMIM10L2B):​c.222A>G​(p.Gln74Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 718,628 control chromosomes in the GnomAD database, including 7 homozygotes. There are 239 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., 46 hem., cov: 24)
  • Exomes 𝑓: 0.0011 (7 hom. 193 hem.)
• Consequence: SMIM10L2B NM_001348255.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19

Genes affected

SMIM10L2B (HGNC:34500): (small integral membrane protein 10 like 2B)

SMIM10L2B-AS1 (HGNC:53137): (SMIM10L2B antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-135098412-T-C is Benign according to our data. Variant chrX-135098412-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM10L2B	NM_001348255.2	c.222A>G	p.Gln74Gln	synonymous_variant	Exon 1 of 2	ENST00000433425.4	NP_001335184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM10L2B	ENST00000433425.4	c.222A>G	p.Gln74Gln	synonymous_variant	Exon 1 of 2	1	NM_001348255.2	ENSP00000487709.1
SMIM10L2B-AS1	ENST00000608079.5	n.51-22115T>C		intron_variant	Intron 1 of 2	3		ENSP00000520616.1

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 122 AN: 110171 Hom.: 0 Cov.: 24 AF XY: 0.00138 AC XY: 46 AN XY: 33215

Gnomad AFR AF: 0.000132

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00274

Gnomad ASJ AF: 0.0114

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000516

Gnomad MID AF: 0.00467

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.00537

GnomAD4 exome AF: 0.00111 AC: 676 AN: 608411 Hom.: 7 Cov.: 9 AF XY: 0.00126 AC XY: 193 AN XY: 152715

Gnomad4 AFR exome AF: 0.000144

Gnomad4 AMR exome AF: 0.000483

Gnomad4 ASJ exome AF: 0.0137

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000283

Gnomad4 FIN exome AF: 0.000909

Gnomad4 NFE exome AF: 0.000896

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.00111 AC: 122 AN: 110217 Hom.: 0 Cov.: 24 AF XY: 0.00138 AC XY: 46 AN XY: 33271

Gnomad4 AFR AF: 0.000132

Gnomad4 AMR AF: 0.00273

Gnomad4 ASJ AF: 0.0114

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000516

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.00529

Alfa AF: 0.00108 Hom.: 7

Bravo AF: 0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMIM10L2B: PP3, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.79		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.79		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs782529285; hg19: chrX-134232442;