22-44311146-A-G

Position:

• chr22-44311146-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001099294.2(SHISAL1):​c.-33+1605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 151,912 control chromosomes in the GnomAD database, including 59,453 homozygotes. 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: 𝑓 0.88 (59453 hom., cov: 29)
• Consequence: SHISAL1 NM_001099294.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

Genes affected

SHISAL1 (HGNC:29335): (shisa like 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SHISAL1	NM_001099294.2	c.-33+1605T>C		intron_variant		ENST00000381176.5	NP_001092764.1
SHISAL1	XM_005261790.4	c.-32-10169T>C		intron_variant			XP_005261847.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SHISAL1	ENST00000381176.5	c.-33+1605T>C		intron_variant		5	NM_001099294.2	ENSP00000370568	P1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134202 AN: 151794 Hom.: 59403 Cov.: 29

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.886

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.884 AC: 134311 AN: 151912 Hom.: 59453 Cov.: 29 AF XY: 0.882 AC XY: 65500 AN XY: 74230

Gnomad4 AFR AF: 0.842

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.889

Gnomad4 FIN AF: 0.856

Gnomad4 NFE AF: 0.912

Gnomad4 OTH AF: 0.888

Alfa AF: 0.892 Hom.: 8237

Bravo AF: 0.884

Asia WGS AF: 0.895 AC: 3109 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.8
DANN	Benign	0.69

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: rs7510759; hg19: chr22-44707026;