rs148716417

Variant names:

• chr2-206751028-C-A
• rs148716417
• NM_001039845.3:c.958G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-206751028-C-A
• chr2-206751028-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001039845.3(MDH1B):​c.958G>T​(p.Val320Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000577 in 1,608,208 control chromosomes in the GnomAD database, including 2 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 0.00040 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (1 hom.)
• Consequence: MDH1B NM_001039845.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.267
• Publications: 4 publications found

Genes affected

MDH1B (HGNC:17836): (malate dehydrogenase 1B) Predicted to enable L-malate dehydrogenase activity. Predicted to be involved in NADH metabolic process; dicarboxylic acid metabolic process; and tricarboxylic acid cycle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.087547034).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039845.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDH1B	NM_001039845.3	MANE Select	c.958G>T	p.Val320Phe	missense	Exon 6 of 12	NP_001034934.1	Q5I0G3-1
	MDH1B	NM_001282940.2		c.958G>T	p.Val320Phe	missense	Exon 6 of 12	NP_001269869.1	Q5I0G3-2
	MDH1B	NM_001330223.2		c.664G>T	p.Val222Phe	missense	Exon 5 of 11	NP_001317152.1	C9JER5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MDH1B	ENST00000374412.8	TSL:1 MANE Select	c.958G>T	p.Val320Phe	missense	Exon 6 of 12	ENSP00000363533.3	Q5I0G3-1
	MDH1B	ENST00000432911.5	TSL:1	n.414-1845G>T		intron	N/A	ENSP00000392464.1	Q5I0G3-3
	MDH1B	ENST00000454776.6	TSL:2	c.958G>T	p.Val320Phe	missense	Exon 6 of 12	ENSP00000389916.2	Q5I0G3-2

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152076 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000384 AC: 96 AN: 250200 AF XY: 0.000333

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000351

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000529

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000595 AC: 867 AN: 1456014 Hom.: 1 Cov.: 29 AF XY: 0.000577 AC XY: 418 AN XY: 724342

African (AFR) AF: 0.000120 AC: 4 AN: 33372

American (AMR) AF: 0.000359 AC: 16 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 55 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53184

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.000683 AC: 757 AN: 1108106

Other (OTH) AF: 0.000566 AC: 34 AN: 60106

GnomAD4 genome AF: 0.000401 AC: 61 AN: 152194 Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74392

African (AFR) AF: 0.000168 AC: 7 AN: 41544

American (AMR) AF: 0.000393 AC: 6 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000620 Hom.: 0

Bravo AF: 0.000495

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000371 AC: 45

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.9	M
PhyloP100		-0.27
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.27
Sift	Benign	0.11	T
Sift4G	Benign	0.20	T
Polyphen		0.22	B
Vest4		0.79
MVP		0.29
MPC		0.26
ClinPred		0.019	T
GERP RS		-2.7
Varity_R		0.11
gMVP		0.92
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs148716417; hg19: chr2-207615752;