chr3-183817188-G-T

Variant names:

• chr3-183817188-G-T
• rs2255015
• NM_024871.4:c.*168C>A

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.*168C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 482,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAP6D1 NM_024871.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.838
• 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 (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP6D1	NM_024871.4	MANE Select	c.*168C>A		3_prime_UTR	Exon 3 of 3	NP_079147.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP6D1	ENST00000318631.8	TSL:1 MANE Select	c.*168C>A		3_prime_UTR	Exon 3 of 3	ENSP00000314560.4
	ENSG00000283765	ENST00000639401.1	TSL:5	c.*168C>A		3_prime_UTR	Exon 11 of 11	ENSP00000491227.1
	MAP6D1	ENST00000933005.1		c.*168C>A		3_prime_UTR	Exon 4 of 4	ENSP00000603064.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 1 AN: 482368 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 254316

⚠️ 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: 13238

American (AMR) AF: 0.00 AC: 0 AN: 22352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14488

East Asian (EAS) AF: 0.00 AC: 0 AN: 29644

South Asian (SAS) AF: 0.00 AC: 0 AN: 48954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2046

European-Non Finnish (NFE) AF: 0.00000340 AC: 1 AN: 294000

Other (OTH) AF: 0.00 AC: 0 AN: 26704

⚠️ 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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.46
PhyloP100		-0.84

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: rs2255015; hg19: chr3-183534976;