rs5932684

Variant names:

• chrX-129791180-T-C
• rs5932684
• NM_018990.4:c.442+99T>C

Your query was ambiguous. Multiple possible variants found:

• chrX-129791180-T-C
• chrX-129791180-T-G

Variant summary

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

The NM_018990.4(SASH3):​c.442+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 803,604 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000012 (0 hom. 0 hem.)
• Consequence: SASH3 NM_018990.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 2 publications found

Genes affected

SASH3 (HGNC:15975): (SAM and SH3 domain containing 3) The protein encoded by this gene contains a Src homology-3 (SH3) domain and a sterile alpha motif (SAM), both of which are found in proteins involved in cell signaling. This protein may function as a signaling adapter protein in lymphocytes.[provided by RefSeq, Sep 2009]

SASH3 Gene-Disease associations (from GenCC):

• immunodeficiency 102

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• combined immunodeficiency, X-linked

  Inheritance: XL Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SASH3	NM_018990.4	c.442+99T>C		intron_variant	Intron 4 of 7	ENST00000356892.4	NP_061863.1
SASH3	XM_006724763.1	c.442+99T>C		intron_variant	Intron 4 of 6		XP_006724826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SASH3	ENST00000356892.4	c.442+99T>C		intron_variant	Intron 4 of 7	1	NM_018990.4	ENSP00000349359.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000124 AC: 1 AN: 803604 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 201302

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000503 AC: 1 AN: 19884

American (AMR) AF: 0.00 AC: 0 AN: 25885

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14086

East Asian (EAS) AF: 0.00 AC: 0 AN: 28019

South Asian (SAS) AF: 0.00 AC: 0 AN: 39873

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2176

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 600386

Other (OTH) AF: 0.00 AC: 0 AN: 35857

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 16247

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.70
PhyloP100		0.0040

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: rs5932684; hg19: chrX-128925156;