3-183825243-G-T

Variant names:

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

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>A​(p.Ala102Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000894 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: 0.0000089 (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=0.09744674).

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>A	p.Ala102Glu	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>A	p.Ala102Glu	missense	Exon 1 of 3	ENSP00000314560.4	Q9H9H5
	ENSG00000283765	ENST00000639401.1	TSL:5	c.1029-7132C>A		intron	N/A	ENSP00000491227.1	A0A1W2PP11
	MAP6D1	ENST00000933005.1		c.305C>A	p.Ala102Glu	missense	Exon 1 of 4	ENSP00000603064.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000894 AC: 11 AN: 1230594 Hom.: 0 Cov.: 30 AF XY: 0.0000117 AC XY: 7 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: 0.00 AC: 0 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: 0.0000110 AC: 11 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.54
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.25
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.050
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.11
MutPred		0.20		Loss of MoRF binding (P = 0.015)
MVP		0.22
MPC		0.042
ClinPred		0.28	T
GERP RS		0.15
PromoterAI		0.0058	Neutral
Varity_R		0.16
gMVP		0.14
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;