NM_017754.4:c.683A>T

Variant names:

• chr6-34835307-A-T
• rs1765649848
• NM_017754.4:c.683A>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_017754.4(BLTP3A):​c.683A>T​(p.Asn228Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N228S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLTP3A NM_017754.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.27
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.762

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3A	NM_017754.4	c.683A>T	p.Asn228Ile	missense_variant	Exon 7 of 21	ENST00000192788.6	NP_060224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP3A	ENST00000192788.6	c.683A>T	p.Asn228Ile	missense_variant	Exon 7 of 21	1	NM_017754.4	ENSP00000192788.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461728 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727160

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111942

Other (OTH) AF: 0.00 AC: 0 AN: 60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	.;M
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-5.2	D;D
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.99	.;D
Vest4		0.85
MutPred		0.42		Loss of catalytic residue at N228 (P = 0.0395);Loss of catalytic residue at N228 (P = 0.0395);
MVP		0.43
MPC		0.66
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.80
gMVP		0.68
Mutation Taster		=66/34	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1765649848; hg19: chr6-34803084;