NM_018990.4:c.442+99T>C

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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

Gnomad4 AFR exome AF: 0.0000503

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

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

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: rs5932684; hg19: chrX-128925156;