rs2644744

Variant names:

• chr5-154931675-T-A
• rs2644744
• NM_015465.5:c.662-98A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-154931675-T-A
• chr5-154931675-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015465.5(GEMIN5):​c.662-98A>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GEMIN5 NM_015465.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 1 publications found

Genes affected

GEMIN5 (HGNC:20043): (gem nuclear organelle associated protein 5) This gene encodes a WD repeat protein that is a component of the survival of motor neurons (SMN) complex. The SMN complex plays a critical role in mRNA splicing through the assembly of spliceosomal small nuclear ribonucleoproteins (snRNPs), and may also mediate the assembly and transport of other classes of ribonucleoproteins. The encoded protein is the snRNA-binding component of the SMN complex. Dysregulation of this gene may play a role in alternative mRNA splicing and tumor cell motility. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

GEMIN5 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with cerebellar atrophy and motor dysfunction

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

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=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GEMIN5	NM_015465.5	c.662-98A>T		intron_variant	Intron 4 of 27	ENST00000285873.8	NP_056280.2
GEMIN5	NM_001252156.2	c.662-101A>T		intron_variant	Intron 4 of 27		NP_001239085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN5	ENST00000285873.8	c.662-98A>T		intron_variant	Intron 4 of 27	1	NM_015465.5	ENSP00000285873.6
GEMIN5	ENST00000523355.1	n.42A>T		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 802236 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 409598

African (AFR) AF: 0.00 AC: 0 AN: 19142

American (AMR) AF: 0.00 AC: 0 AN: 26132

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16914

East Asian (EAS) AF: 0.00 AC: 0 AN: 34946

South Asian (SAS) AF: 0.00 AC: 0 AN: 56020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43864

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 564108

Other (OTH) AF: 0.00 AC: 0 AN: 37350

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		1.2

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: rs2644744; hg19: chr5-154311235;