14-103405174-A-C

Variant names:

• chr14-103405174-A-C
• NM_001128918.3:c.150A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128918.3(MARK3):​c.150A>C​(p.Gln50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,447,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MARK3 NM_001128918.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

Genes affected

MARK3 (HGNC:6897): (microtubule affinity regulating kinase 3) The protein encoded by this gene is activated by phosphorylation and in turn is involved in the phosphorylation of tau proteins MAP2 and MAP4. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15364522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARK3	NM_001128918.3	c.150A>C	p.Gln50His	missense_variant	Exon 2 of 18	ENST00000429436.7	NP_001122390.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARK3	ENST00000429436.7	c.150A>C	p.Gln50His	missense_variant	Exon 2 of 18	1	NM_001128918.3	ENSP00000411397.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000345 AC: 5 AN: 1447508 Hom.: 0 Cov.: 30 AF XY: 0.00000555 AC XY: 4 AN XY: 720102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Uncertain	0.56	.;.;D;.;.;.;T;.;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.4	L;L;L;L;L;L;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;N;D
REVEL	Benign	0.19
Sift	Uncertain	0.0040	D;T;T;T;T;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T;T;T;T;T
Polyphen		0.035, 0.0070, 0.029, 0.0060	.;B;B;B;B;B;.;.;.
Vest4		0.39
MutPred		0.34		Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);Gain of catalytic residue at A47 (P = 0.0072);.;
MVP		0.61
MPC		0.29
ClinPred		0.41	T
GERP RS		-3.5
Varity_R		0.56
gMVP		0.56

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-103871511;