rs13205210

Positions:

• chr6-34864079-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017754.4(BLTP3A):​c.3293T>C​(p.Met1098Thr) variant causes a missense change. The variant allele was found at a frequency of 0.111 in 1,613,362 control chromosomes in the GnomAD database, including 10,672 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1537 hom., cov: 31)
  • Exomes 𝑓: 0.11 (9135 hom.)
• Consequence: BLTP3A NM_017754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.01

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017387867).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BLTP3A	NM_017754.4	c.3293T>C	p.Met1098Thr	missense_variant	15/21	ENST00000192788.6	NP_060224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BLTP3A	ENST00000192788.6	c.3293T>C	p.Met1098Thr	missense_variant	15/21	1	NM_017754.4	ENSP00000192788.5

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20172 AN: 151910 Hom.: 1529 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.154

GnomAD3 exomes AF: 0.111 AC: 27725 AN: 249218 Hom.: 1710 AF XY: 0.113 AC XY: 15323 AN XY: 135202

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.0817

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.117

Gnomad FIN exome AF: 0.0587

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.108 AC: 158452 AN: 1461334 Hom.: 9135 Cov.: 38 AF XY: 0.109 AC XY: 79558 AN XY: 726944

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.0839

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0894

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0584

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.123

GnomAD4 genome AF: 0.133 AC: 20205 AN: 152028 Hom.: 1537 Cov.: 31 AF XY: 0.132 AC XY: 9842 AN XY: 74318

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.155

Alfa AF: 0.121 Hom.: 2933

Bravo AF: 0.142

TwinsUK AF: 0.115 AC: 428

ALSPAC AF: 0.102 AC: 393

ESP6500AA AF: 0.193 AC: 778

ESP6500EA AF: 0.111 AC: 924

ExAC AF: 0.114 AC: 13759

Asia WGS AF: 0.133 AC: 463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	D;D
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.83	.;P
Vest4		0.24
MPC		0.52
ClinPred		0.036	T
GERP RS		6.0
Varity_R		0.61
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs13205210; hg19: chr6-34831856; COSMIC: COSV51955648;