NM_001352514.2:c.*3223_*3226dupTTTT

Variant names:

• chr21-36751019-C-CAAAA
• rs35955622
• NM_001352514.2:c.*3223_*3226dupTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001352514.2(HLCS):​c.*3223_*3226dupTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000036 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLCS NM_001352514.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208

Genes affected

HLCS (HGNC:4976): (holocarboxylase synthetase) This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLCS	NM_001352514.2	c.*3223_*3226dupTTTT		3_prime_UTR_variant	Exon 11 of 11	ENST00000674895.3	NP_001339443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLCS	ENST00000674895	c.*3223_*3226dupTTTT		3_prime_UTR_variant	Exon 11 of 11		NM_001352514.2	ENSP00000502087.2
HLCS	ENST00000336648	c.*3223_*3226dupTTTT		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000338387.3
HLCS	ENST00000612277	c.*3223_*3226dupTTTT		3_prime_UTR_variant	Exon 12 of 12	5		ENSP00000479939.1
HLCS	ENST00000399120.5	c.*3223_*3226dupTTTT		downstream_gene_variant		1		ENSP00000382071.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 5 AN: 139398 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.0000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000156

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 68 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 34

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000359 AC: 5 AN: 139398 Hom.: 0 Cov.: 30 AF XY: 0.0000743 AC XY: 5 AN XY: 67304

Gnomad4 AFR AF: 0.0000263

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.0000156

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs35955622; hg19: chr21-38123320;