NM_017754.4:c.1735T>C

Variant names:

• chr6-34857885-T-C
• rs16894959
• NM_017754.4:c.1735T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017754.4(BLTP3A):​c.1735T>C​(p.Leu579Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,613,712 control chromosomes in the GnomAD database, including 17,853 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 0.17 (2597 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15256 hom.)
• Consequence: BLTP3A NM_017754.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.431
• Publications: 32 publications found

Genes affected

BLTP3A (HGNC:21216): (bridge-like lipid transfer protein family member 3A) Enables histone deacetylase binding activity and identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.431 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017754.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP3A	NM_017754.4	MANE Select	c.1735T>C	p.Leu579Leu	synonymous	Exon 13 of 21	NP_060224.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP3A	ENST00000192788.6	TSL:1 MANE Select	c.1735T>C	p.Leu579Leu	synonymous	Exon 13 of 21	ENSP00000192788.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26422 AN: 151990 Hom.: 2593 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.131 AC: 32626 AN: 249234 AF XY: 0.129

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0802

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.0135

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.133

GnomAD4 exome AF: 0.138 AC: 202302 AN: 1461604 Hom.: 15256 Cov.: 33 AF XY: 0.137 AC XY: 99503 AN XY: 727082

African (AFR) AF: 0.260 AC: 8693 AN: 33478

American (AMR) AF: 0.0860 AC: 3844 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 4077 AN: 26134

East Asian (EAS) AF: 0.00658 AC: 261 AN: 39690

South Asian (SAS) AF: 0.0772 AC: 6663 AN: 86258

European-Finnish (FIN) AF: 0.204 AC: 10894 AN: 53272

Middle Eastern (MID) AF: 0.129 AC: 744 AN: 5768

European-Non Finnish (NFE) AF: 0.143 AC: 158774 AN: 1111894

Other (OTH) AF: 0.138 AC: 8352 AN: 60390

GnomAD4 genome AF: 0.174 AC: 26440 AN: 152108 Hom.: 2597 Cov.: 32 AF XY: 0.175 AC XY: 12990 AN XY: 74370

African (AFR) AF: 0.254 AC: 10546 AN: 41470

American (AMR) AF: 0.124 AC: 1896 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 566 AN: 3470

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5182

South Asian (SAS) AF: 0.0793 AC: 383 AN: 4828

European-Finnish (FIN) AF: 0.214 AC: 2268 AN: 10578

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10188 AN: 67996

Other (OTH) AF: 0.158 AC: 333 AN: 2108

Alfa AF: 0.154 Hom.: 2037

Bravo AF: 0.172

Asia WGS AF: 0.0490 AC: 172 AN: 3478

EpiCase AF: 0.143

EpiControl AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.53
PhyloP100		-0.43
Mutation Taster		=97/3	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: rs16894959; hg19: chr6-34825662; COSMIC: COSV51955817;