rs10509373

Variant names:

• chr10-76397814-T-C
• rs10509373
• NM_001305581.2:c.601+73329T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305581.2(LRMDA):​c.601+73329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 151,904 control chromosomes in the GnomAD database, including 9,767 homozygotes. 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: 𝑓 0.32 (9767 hom., cov: 33)
• Consequence: LRMDA NM_001305581.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 18 publications found

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

LRMDA Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 7

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.601+73329T>C		intron_variant	Intron 6 of 6	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.517+73329T>C		intron_variant	Intron 5 of 5		NP_114413.1
LRMDA	NR_131178.2	n.955+73329T>C		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.601+73329T>C		intron_variant	Intron 6 of 6	5	NM_001305581.2	ENSP00000480240.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48113 AN: 151786 Hom.: 9769 Cov.: 33

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.317 AC: 48105 AN: 151904 Hom.: 9767 Cov.: 33 AF XY: 0.312 AC XY: 23145 AN XY: 74268

African (AFR) AF: 0.0832 AC: 3434 AN: 41292

American (AMR) AF: 0.408 AC: 6240 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1286 AN: 3458

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5182

South Asian (SAS) AF: 0.190 AC: 914 AN: 4814

European-Finnish (FIN) AF: 0.376 AC: 3976 AN: 10578

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30882 AN: 67980

Other (OTH) AF: 0.331 AC: 698 AN: 2110

Alfa AF: 0.406 Hom.: 38542

Bravo AF: 0.310

Asia WGS AF: 0.119 AC: 415 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs10509373; hg19: chr10-78157572;