NM_017754.4:c.473A>G

Variant names:

• chr6-34834351-A-G
• rs199768762
• NM_017754.4:c.473A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_017754.4(BLTP3A):​c.473A>G​(p.Asn158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,613,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: BLTP3A NM_017754.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.05
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.028221577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3A	NM_017754.4	c.473A>G	p.Asn158Ser	missense_variant	Exon 5 of 21	ENST00000192788.6	NP_060224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP3A	ENST00000192788.6	c.473A>G	p.Asn158Ser	missense_variant	Exon 5 of 21	1	NM_017754.4	ENSP00000192788.5

Frequencies

GnomAD3 genomes AF: 0.000177 AC: 27 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000269 AC: 67 AN: 249412 AF XY: 0.000266

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000348

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.000126 AC: 184 AN: 1461644 Hom.: 1 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 727144

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.000313 AC: 14 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00218 AC: 57 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86240

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

Middle Eastern (MID) AF: 0.00321 AC: 18 AN: 5606

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111976

Other (OTH) AF: 0.000315 AC: 19 AN: 60376

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74364

African (AFR) AF: 0.000193 AC: 8 AN: 41450

American (AMR) AF: 0.000196 AC: 3 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000329 Hom.: 0

Bravo AF: 0.000272

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000481 AC: 4

ExAC AF: 0.000265 AC: 32

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473A>G (p.N158S) alteration is located in exon 5 (coding exon 5) of the UHRF1BP1 gene. This alteration results from a A to G substitution at nucleotide position 473, causing the asparagine (N) at amino acid position 158 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.4
DANN	Benign	0.86
DEOGEN2	Benign	0.019	T;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.92
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.028	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.95	.;L
PhyloP100		1.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.051
Sift	Benign	0.28	T;T
Sift4G	Benign	0.59	T;T
Polyphen		0.020	.;B
Vest4		0.10
MVP		0.23
MPC		0.10
ClinPred		0.0020	T
GERP RS		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.059
Mutation Taster		=98/2	polymorphism

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: rs199768762; hg19: chr6-34802128;