chr21-36751103-A-AAT

Position:

• chr21-36751103-A-AAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001352514.2(HLCS):​c.*3142_*3143insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (12633 hom., cov: 0)
  • Exomes 𝑓: 0.32 (21 hom.)
• Consequence: HLCS NM_001352514.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.777

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 21-36751103-A-AAT is Benign according to our data. Variant chr21-36751103-A-AAT is described in ClinVar as [Benign]. Clinvar id is 339915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLCS	NM_001352514.2	c.*3142_*3143insAT		3_prime_UTR_variant	11/11	ENST00000674895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLCS	ENST00000674895.3	c.*3142_*3143insAT		3_prime_UTR_variant	11/11		NM_001352514.2	P4
HLCS	ENST00000336648.8	c.*3142_*3143insAT		3_prime_UTR_variant	12/12	1		A1
HLCS	ENST00000612277.4	c.*3142_*3143insAT		3_prime_UTR_variant	12/12	5		A1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61435 AN: 151666 Hom.: 12611 Cov.: 0

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.321 AC: 134 AN: 418 Hom.: 21 Cov.: 0 AF XY: 0.324 AC XY: 83 AN XY: 256

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.405 AC: 61479 AN: 151784 Hom.: 12633 Cov.: 0 AF XY: 0.402 AC XY: 29802 AN XY: 74172

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.425

Alfa AF: 0.403 Hom.: 1288

Asia WGS AF: 0.304 AC: 1054 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Holocarboxylase synthetase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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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: rs3031056; hg19: chr21-38123404;