NM_024871.4:c.343G>T

Variant names:

• chr3-183825205-C-A
• rs1019462828
• NM_024871.4:c.343G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024871.4(MAP6D1):​c.343G>T​(p.Val115Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,442,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. V115I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000031 (0 hom.)
• Consequence: MAP6D1 NM_024871.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 0 publications found

Genes affected

MAP6D1 (HGNC:25753): (MAP6 domain containing 1) This gene encodes a protein highly similar to the mouse MAP6 domain containing 1 protein, which is related to the STOP proteins. Based on the study of the mouse protein, the encoded protein may function as a calmodulin-regulated neuronal protein that binds and stabilizes microtubules but also associates with the Golgi membranes through N-terminal palmitoylation. [provided by RefSeq, Oct 2008]

ENSG00000283765 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.092006266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024871.4. 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
	MAP6D1	NM_024871.4	MANE Select	c.343G>T	p.Val115Phe	missense	Exon 1 of 3	NP_079147.1	Q9H9H5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP6D1	ENST00000318631.8	TSL:1 MANE Select	c.343G>T	p.Val115Phe	missense	Exon 1 of 3	ENSP00000314560.4	Q9H9H5
	ENSG00000283765	ENST00000639401.1	TSL:5	c.1029-7094G>T		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	MAP6D1	ENST00000933005.1		c.343G>T	p.Val115Phe	missense	Exon 1 of 4	ENSP00000603064.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000310 AC: 4 AN: 1290640 Hom.: 0 Cov.: 30 AF XY: 0.00000473 AC XY: 3 AN XY: 634452

African (AFR) AF: 0.00 AC: 0 AN: 25856

American (AMR) AF: 0.00 AC: 0 AN: 19746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21772

East Asian (EAS) AF: 0.00 AC: 0 AN: 27792

South Asian (SAS) AF: 0.00 AC: 0 AN: 64052

European-Finnish (FIN) AF: 0.0000442 AC: 2 AN: 45232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5302

European-Non Finnish (NFE) AF: 0.00000195 AC: 2 AN: 1028066

Other (OTH) AF: 0.00 AC: 0 AN: 52822

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

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

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.098
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.045
Sift	Benign	0.063	T
Sift4G	Benign	0.28	T
Polyphen		0.014	B
Vest4		0.26
MutPred		0.23		Loss of phosphorylation at Y116 (P = 0.1227)
MVP		0.099
MPC		0.044
ClinPred		0.37	T
GERP RS		0.72
PromoterAI		0.0057	Neutral
Varity_R		0.16
gMVP		0.24
Mutation Taster		=100/0	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: rs1019462828; hg19: chr3-183542993;