NM_024871.4:c.151G>C

Variant names:

• chr3-183825397-C-G
• rs959769906
• NM_024871.4:c.151G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024871.4(MAP6D1):​c.151G>C​(p.Gly51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000691 in 1,447,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: MAP6D1 NM_024871.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.91
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052046537).

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.151G>C	p.Gly51Arg	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.151G>C	p.Gly51Arg	missense	Exon 1 of 3	ENSP00000314560.4	Q9H9H5
	ENSG00000283765	ENST00000639401.1	TSL:5	c.1029-7286G>C		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	MAP6D1	ENST00000933005.1		c.151G>C	p.Gly51Arg	missense	Exon 1 of 4	ENSP00000603064.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151542 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 1 AN: 62590 AF XY: 0.0000275

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000452

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000756 AC: 98 AN: 1295630 Hom.: 0 Cov.: 30 AF XY: 0.0000595 AC XY: 38 AN XY: 638124

African (AFR) AF: 0.00 AC: 0 AN: 25828

American (AMR) AF: 0.00 AC: 0 AN: 21840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21670

East Asian (EAS) AF: 0.00 AC: 0 AN: 27414

South Asian (SAS) AF: 0.00 AC: 0 AN: 68336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37896

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3790

European-Non Finnish (NFE) AF: 0.0000927 AC: 96 AN: 1035670

Other (OTH) AF: 0.0000376 AC: 2 AN: 53186

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151542 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74018

African (AFR) AF: 0.0000242 AC: 1 AN: 41364

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10408

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

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67778

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

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	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.8
DANN	Benign	0.64
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.46	N
PhyloP100		-1.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.011
Sift	Benign	0.17	T
Sift4G	Benign	0.78	T
Polyphen		0.0030	B
Vest4		0.080
MutPred		0.18		Gain of solvent accessibility (P = 0.0097)
MVP		0.13
MPC		0.020
ClinPred		0.047	T
GERP RS		0.47
PromoterAI		0.29	Neutral
Varity_R		0.040
gMVP		0.13
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: rs959769906; hg19: chr3-183543185;