3-183825243-G-C

Variant names:

• chr3-183825243-G-C
• rs760667646
• NM_024871.4:c.305C>G

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.305C>G​(p.Ala102Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000244 in 1,230,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A102T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: MAP6D1 NM_024871.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249
• 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=0.07046309).

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.305C>G	p.Ala102Gly	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.305C>G	p.Ala102Gly	missense	Exon 1 of 3	ENSP00000314560.4	Q9H9H5
	ENSG00000283765	ENST00000639401.1	TSL:5	c.1029-7132C>G		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	MAP6D1	ENST00000933005.1		c.305C>G	p.Ala102Gly	missense	Exon 1 of 4	ENSP00000603064.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000431 AC: 1 AN: 23208 AF XY: 0.0000761

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: 0.000148

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000244 AC: 3 AN: 1230594 Hom.: 0 Cov.: 30 AF XY: 0.00000167 AC XY: 1 AN XY: 599590

African (AFR) AF: 0.00 AC: 0 AN: 24476

American (AMR) AF: 0.00 AC: 0 AN: 12192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17960

East Asian (EAS) AF: 0.00 AC: 0 AN: 27392

South Asian (SAS) AF: 0.0000194 AC: 1 AN: 51456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4854

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 1000540

Other (OTH) AF: 0.00 AC: 0 AN: 50198

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.4
DANN	Benign	0.68
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.25
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.059
Sift	Benign	0.035	D
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.034
MutPred		0.15		Gain of catalytic residue at A102 (P = 0.0414)
MVP		0.19
MPC		0.035
ClinPred		0.12	T
GERP RS		0.15
PromoterAI		0.013	Neutral
Varity_R		0.094
gMVP		0.11
Mutation Taster		=99/1	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: rs760667646; hg19: chr3-183543031;