3-121645326-A-T

Variant names:

• chr3-121645326-A-T
• rs1919550
• NM_005335.6:c.289-398T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005335.6(HCLS1):​c.289-398T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0848 in 152,236 control chromosomes in the GnomAD database, including 1,197 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 0.085 (1197 hom., cov: 32)
• Consequence: HCLS1 NM_005335.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• Publications: 6 publications found

Genes affected

HCLS1 (HGNC:4844): (hematopoietic cell-specific Lyn substrate 1) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity and protein kinase binding activity. Involved in several processes, including positive regulation of intracellular signal transduction; positive regulation of protein phosphorylation; and regulation of transcription, DNA-templated. Located in cytosol; nucleus; and plasma membrane. Part of transcription regulator complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCLS1	NM_005335.6	c.289-398T>A		intron_variant	Intron 4 of 13	ENST00000314583.8	NP_005326.3
HCLS1	NM_001292041.2	c.289-398T>A		intron_variant	Intron 4 of 12		NP_001278970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCLS1	ENST00000314583.8	c.289-398T>A		intron_variant	Intron 4 of 13	1	NM_005335.6	ENSP00000320176.3

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12882 AN: 152118 Hom.: 1183 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.0815

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0908

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0829

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0848 AC: 12909 AN: 152236 Hom.: 1197 Cov.: 32 AF XY: 0.0900 AC XY: 6702 AN XY: 74448

African (AFR) AF: 0.0197 AC: 820 AN: 41558

American (AMR) AF: 0.291 AC: 4442 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3468

East Asian (EAS) AF: 0.0819 AC: 424 AN: 5180

South Asian (SAS) AF: 0.0466 AC: 225 AN: 4830

European-Finnish (FIN) AF: 0.0908 AC: 963 AN: 10602

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0829 AC: 5635 AN: 68004

Other (OTH) AF: 0.0801 AC: 169 AN: 2110

Alfa AF: 0.0862 Hom.: 120

Bravo AF: 0.0992

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.54
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1919550; hg19: chr3-121364173;