rs1379752462

Variant names:

• chr10-99879936-C-A
• rs1379752462
• NM_015221.4:c.4423G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-99879936-C-A
• chr10-99879936-C-G
• chr10-99879936-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015221.4(DNMBP):​c.4423G>T​(p.Val1475Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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. V1475I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNMBP NM_015221.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.935

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073093176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4	c.4423G>T	p.Val1475Phe	missense_variant	Exon 16 of 17	ENST00000324109.9	NP_056036.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMBP	ENST00000324109.9	c.4423G>T	p.Val1475Phe	missense_variant	Exon 16 of 17	1	NM_015221.4	ENSP00000315659.4
DNMBP	ENST00000543621.6	c.2287G>T	p.Val763Phe	missense_variant	Exon 13 of 14	1		ENSP00000443657.2
DNMBP	ENST00000636706.1	c.3319G>T	p.Val1107Phe	missense_variant	Exon 13 of 14	2		ENSP00000489875.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.7
DANN	Benign	0.92
DEOGEN2	Benign	0.037	.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.073	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;.;M
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N;.;N
REVEL	Benign	0.012
Sift	Uncertain	0.0030	D;.;T
Sift4G	Benign	0.36	.;.;T
Polyphen		0.20	.;.;B
Vest4		0.27
MVP		0.31
MPC		0.25
ClinPred		0.088	T
GERP RS		2.3
Varity_R		0.10
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1379752462; hg19: chr10-101639693;