NM_173489.5:c.2241+8_2241+9insAAA

Variant names:

• chr5-41033829-C-CTTT
• rs70988830
• NM_173489.5:c.2241+8_2241+9insAAA

Variant summary

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

The NM_173489.5(MROH2B):​c.2241+8_2241+9insAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000226 in 1,324,896 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (1 hom., cov: 0)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: MROH2B NM_173489.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• Publications: 3 publications found

Genes affected

MROH2B (HGNC:26857): (maestro heat like repeat family member 2B) Predicted to be involved in protein kinase A signaling. Predicted to be located in acrosomal vesicle and sperm midpiece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MROH2B	NM_173489.5	c.2241+8_2241+9insAAA		splice_region_variant, intron_variant	Intron 22 of 41	ENST00000399564.5	NP_775760.3
MROH2B	XM_011513952.2	c.2241+8_2241+9insAAA		splice_region_variant, intron_variant	Intron 22 of 42		XP_011512254.1
MROH2B	XM_011513953.2	c.2055+8_2055+9insAAA		splice_region_variant, intron_variant	Intron 21 of 40		XP_011512255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MROH2B	ENST00000399564.5	c.2241+8_2241+9insAAA		splice_region_variant, intron_variant	Intron 22 of 41	1	NM_173489.5	ENSP00000382476.4
MROH2B	ENST00000506092.6	c.906+8_906+9insAAA		splice_region_variant, intron_variant	Intron 12 of 31	2		ENSP00000441504.1
MROH2B	ENST00000503890.5	n.1203+8_1203+9insAAA		splice_region_variant, intron_variant	Intron 10 of 30	2
MROH2B	ENST00000515297.5	n.1629+8_1629+9insAAA		splice_region_variant, intron_variant	Intron 16 of 35	5

Frequencies

GnomAD3 genomes AF: 0.0000137 AC: 2 AN: 146062 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000437

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 8.48e-7 AC: 1 AN: 1178834 Hom.: 0 Cov.: 30 AF XY: 0.00000170 AC XY: 1 AN XY: 586890

African (AFR) AF: 0.00 AC: 0 AN: 27640

American (AMR) AF: 0.00 AC: 0 AN: 32796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22206

East Asian (EAS) AF: 0.00 AC: 0 AN: 34806

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5122

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 887732

Other (OTH) AF: 0.00 AC: 0 AN: 50398

GnomAD4 genome AF: 0.0000137 AC: 2 AN: 146062 Hom.: 1 Cov.: 0 AF XY: 0.0000281 AC XY: 2 AN XY: 71180

African (AFR) AF: 0.00 AC: 0 AN: 38830

American (AMR) AF: 0.00 AC: 0 AN: 14658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3336

East Asian (EAS) AF: 0.00 AC: 0 AN: 5058

South Asian (SAS) AF: 0.000437 AC: 2 AN: 4578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66360

Other (OTH) AF: 0.00 AC: 0 AN: 1988

Alfa AF: 0.00 Hom.: 640

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24

Splicing

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

Other links and lift over

dbSNP: rs70988830; hg19: chr5-41033931;