rs13205210

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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1098V) has been classified as Uncertain significance.

• 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	UniProt
BLTP3A	NM_017754.4	c.3293T>C	p.Met1098Thr	missense_variant	15/21	ENST00000192788.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLTP3A	ENST00000192788.6	c.3293T>C	p.Met1098Thr	missense_variant	15/21	1	NM_017754.4	P1

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
MutationTaster	Benign	0.000080	P;P
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;