NM_005335.6:c.*120T>A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005335.6(HCLS1):​c.*120T>A variant causes a 3 prime UTR 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HCLS1 NM_005335.6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005335.6. 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>A		3_prime_UTR	Exon 14 of 14	NP_005326.3
	HCLS1	NM_001292041.2		c.*120T>A		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>A		3_prime_UTR	Exon 14 of 14	ENSP00000320176.3
	HCLS1	ENST00000909628.1		c.*120T>A		3_prime_UTR	Exon 14 of 14	ENSP00000579687.1
	HCLS1	ENST00000909631.1		c.*120T>A		3_prime_UTR	Exon 14 of 14	ENSP00000579690.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 902884 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 456430

African (AFR) AF: 0.00 AC: 0 AN: 21602

American (AMR) AF: 0.00 AC: 0 AN: 28414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17814

East Asian (EAS) AF: 0.00 AC: 0 AN: 34722

South Asian (SAS) AF: 0.00 AC: 0 AN: 60202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3082

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 651840

Other (OTH) AF: 0.00 AC: 0 AN: 40936

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.62
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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;