16-75116377-C-T

Variant names:

• chr16-75116377-C-T
• rs730168
• NM_194436.3:c.72+272G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194436.3(LDHD):​c.72+272G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,038 control chromosomes in the GnomAD database, including 8,818 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 0.31 (8818 hom., cov: 32)
• Consequence: LDHD NM_194436.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 6 publications found

Genes affected

LDHD (HGNC:19708): (lactate dehydrogenase D) The protein encoded by this gene belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family. The similar protein in yeast has both D-lactate and D-glycerate dehydrogenase activities. Alternative splicing occurs at this locus and two transcript variants encoding distinct isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LDHD	NM_194436.3	c.72+272G>A		intron_variant	Intron 1 of 10	ENST00000450168.3	NP_919417.1
LDHD	NM_153486.4	c.72+272G>A		intron_variant	Intron 1 of 10		NP_705690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LDHD	ENST00000450168.3	c.72+272G>A		intron_variant	Intron 1 of 10	1	NM_194436.3	ENSP00000417011.2
LDHD	ENST00000300051.8	c.72+272G>A		intron_variant	Intron 1 of 10	1		ENSP00000300051.4
LDHD	ENST00000569876.2	n.*1+235G>A		intron_variant	Intron 1 of 10	5		ENSP00000454260.1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46403 AN: 151920 Hom.: 8789 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.275

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.306 AC: 46484 AN: 152038 Hom.: 8818 Cov.: 32 AF XY: 0.310 AC XY: 23032 AN XY: 74336

African (AFR) AF: 0.489 AC: 20278 AN: 41436

American (AMR) AF: 0.328 AC: 5013 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 593 AN: 3466

East Asian (EAS) AF: 0.605 AC: 3116 AN: 5154

South Asian (SAS) AF: 0.434 AC: 2094 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1910 AN: 10606

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12574 AN: 67948

Other (OTH) AF: 0.281 AC: 592 AN: 2106

Alfa AF: 0.213 Hom.: 6199

Bravo AF: 0.325

Asia WGS AF: 0.539 AC: 1868 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.41
PhyloP100		-2.0
PromoterAI		-0.11	Neutral
Mutation Taster		=100/0	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: rs730168; hg19: chr16-75150275;