rs1128163

Variant names:

• chr3-121631726-A-G
• rs1128163
• NM_005335.6:c.*120T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-121631726-A-G
• chr3-121631726-A-T

Variant summary

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

The ENST00000314583.8(HCLS1):​c.*120T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,053,022 control chromosomes in the GnomAD database, including 31,156 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 0.23 (4169 hom., cov: 31)
  • Exomes 𝑓: 0.24 (26987 hom.)
• Consequence: HCLS1 ENST00000314583.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 10 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000314583.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCLS1	NM_005335.6	MANE Select	c.*120T>C		3_prime_UTR	Exon 14 of 14	NP_005326.3
	HCLS1	NM_001292041.2		c.*120T>C		3_prime_UTR	Exon 13 of 13	NP_001278970.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCLS1	ENST00000314583.8	TSL:1 MANE Select	c.*120T>C		3_prime_UTR	Exon 14 of 14	ENSP00000320176.3
	HCLS1	ENST00000473883.5	TSL:2	n.2384T>C		non_coding_transcript_exon	Exon 9 of 9
	HCLS1	ENST00000428394.6	TSL:2	c.*120T>C		3_prime_UTR	Exon 13 of 13	ENSP00000387645.2

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34303 AN: 151862 Hom.: 4173 Cov.: 31

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.239 AC: 215004 AN: 901042 Hom.: 26987 Cov.: 12 AF XY: 0.239 AC XY: 108818 AN XY: 455572

African (AFR) AF: 0.166 AC: 3587 AN: 21576

American (AMR) AF: 0.163 AC: 4622 AN: 28392

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 5391 AN: 17794

East Asian (EAS) AF: 0.394 AC: 13677 AN: 34682

South Asian (SAS) AF: 0.231 AC: 13910 AN: 60154

European-Finnish (FIN) AF: 0.213 AC: 9418 AN: 44204

Middle Eastern (MID) AF: 0.334 AC: 1028 AN: 3076

European-Non Finnish (NFE) AF: 0.235 AC: 152716 AN: 650274

Other (OTH) AF: 0.261 AC: 10655 AN: 40890

GnomAD4 genome AF: 0.226 AC: 34300 AN: 151980 Hom.: 4169 Cov.: 31 AF XY: 0.224 AC XY: 16609 AN XY: 74292

African (AFR) AF: 0.170 AC: 7042 AN: 41448

American (AMR) AF: 0.204 AC: 3116 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2294 AN: 5132

South Asian (SAS) AF: 0.216 AC: 1037 AN: 4806

European-Finnish (FIN) AF: 0.211 AC: 2236 AN: 10574

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.245 AC: 16668 AN: 67958

Other (OTH) AF: 0.258 AC: 545 AN: 2116

Alfa AF: 0.233 Hom.: 2012

Bravo AF: 0.225

Asia WGS AF: 0.288 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.0
DANN	Benign	0.63
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1128163; hg19: chr3-121350573; COSMIC: COSV57526052; COSMIC: COSV57526052;