1-36156455-C-A

Variant names:

• chr1-36156455-C-A
• rs745390462
• NM_001388490.1:c.38C>A

Variant summary

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

The NM_001388490.1(MAP7D1):​c.38C>A​(p.Ala13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000759 in 1,318,272 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. A13V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: MAP7D1 NM_001388490.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539
• Publications: 1 publications found

Genes affected

MAP7D1 (HGNC:25514): (MAP7 domain containing 1) Predicted to be involved in microtubule cytoskeleton organization. Located in cytosol and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2096752).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388490.1. 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
	MAP7D1	NM_001388490.1	MANE Select	c.38C>A	p.Ala13Glu	missense	Exon 1 of 17	NP_001375419.1	D3DPS3
	MAP7D1	NM_018067.5		c.38C>A	p.Ala13Glu	missense	Exon 1 of 17	NP_060537.3
	MAP7D1	NM_001286366.2		c.38C>A	p.Ala13Glu	missense	Exon 1 of 18	NP_001273295.1	Q3KQU3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP7D1	ENST00000474796.2	TSL:2 MANE Select	c.38C>A	p.Ala13Glu	missense	Exon 1 of 17	ENSP00000507044.1	D3DPS3
	MAP7D1	ENST00000373151.6	TSL:1	c.38C>A	p.Ala13Glu	missense	Exon 1 of 17	ENSP00000362244.2	Q3KQU3-1
	MAP7D1	ENST00000316156.8	TSL:1	c.38C>A	p.Ala13Glu	missense	Exon 1 of 16	ENSP00000320228.4	Q3KQU3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000150 AC: 1 AN: 66878 AF XY: 0.0000256

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1318272 Hom.: 0 Cov.: 31 AF XY: 0.00000154 AC XY: 1 AN XY: 649706

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

African (AFR) AF: 0.00 AC: 0 AN: 26250

American (AMR) AF: 0.00 AC: 0 AN: 24378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22616

East Asian (EAS) AF: 0.00 AC: 0 AN: 28490

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 72144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1050400

Other (OTH) AF: 0.00 AC: 0 AN: 54746

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0038	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.030
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.54
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.13		Gain of solvent accessibility (P = 0.0674)
MVP		0.043
MPC		0.17
ClinPred		0.35	T
GERP RS		4.0
PromoterAI		0.045	Neutral
Varity_R		0.38
gMVP		0.20
Mutation Taster		=89/11	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: rs745390462; hg19: chr1-36622056;