rs1002554080

Variant names:

• chr3-121632338-G-A
• rs1002554080
• NM_005335.6:c.1234C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-121632338-G-A
• chr3-121632338-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005335.6(HCLS1):​c.1234C>T​(p.Leu412Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: HCLS1 NM_005335.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

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

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.08 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCLS1	NM_005335.6	c.1234C>T	p.Leu412Leu	synonymous_variant	Exon 12 of 14	ENST00000314583.8	NP_005326.3
HCLS1	NM_001292041.2	c.1123C>T	p.Leu375Leu	synonymous_variant	Exon 11 of 13		NP_001278970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCLS1	ENST00000314583.8	c.1234C>T	p.Leu412Leu	synonymous_variant	Exon 12 of 14	1	NM_005335.6	ENSP00000320176.3
HCLS1	ENST00000428394.6	c.1123C>T	p.Leu375Leu	synonymous_variant	Exon 11 of 13	2		ENSP00000387645.2
HCLS1	ENST00000473883.5	n.2037C>T		non_coding_transcript_exon_variant	Exon 7 of 9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.71
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1002554080; hg19: chr3-121351185; COSMIC: COSV105115112; COSMIC: COSV105115112;