chr2-38751622-T-C

Variant names:

• chr2-38751622-T-C
• rs12621103
• ENST00000409011.5:c.-477T>C

Variant summary

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

The ENST00000409011.5(GEMIN6):​c.-477T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 314,408 control chromosomes in the GnomAD database, including 80,447 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 0.71 (38491 hom., cov: 29)
  • Exomes 𝑓: 0.71 (41956 hom.)
• Consequence: GEMIN6 ENST00000409011.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 3 publications found

Genes affected

GEMIN6 (HGNC:20044): (gem nuclear organelle associated protein 6) GEMIN6 is part of a large macromolecular complex, localized to both the cytoplasm and the nucleus, that plays a role in the cytoplasmic assembly of small nuclear ribonucleoproteins (snRNPs). Other members of this complex include SMN (MIM 600354), GEMIN2 (SIP1; MIM 602595), GEMIN3 (DDX20; MIM 606168), GEMIN4 (MIM 606969), and GEMIN5 (MIM 607005).[supplied by OMIM, Jul 2002]

SRSF7 (HGNC:10789): (serine and arginine rich splicing factor 7) The protein encoded by this gene is a member of the serine/arginine (SR)-rich family of pre-mRNA splicing factors, which constitute part of the spliceosome. Each of these factors contains an N-terminal RNA recognition motif (RRM) for binding RNA and a C-terminal RS domain for binding other proteins. The RS domain is rich in serine and arginine residues and facilitates interaction between different SR splicing factors. In addition to being critical for mRNA splicing, the SR proteins have also been shown to be involved in mRNA export from the nucleus and in translation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2018]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRSF7	NM_001363802.1	c.-366A>G		upstream_gene_variant			NP_001350731.1
SRSF7	XM_005264485.3	c.-366A>G		upstream_gene_variant			XP_005264542.1
SRSF7	XR_007079572.1	n.-128A>G		upstream_gene_variant
SRSF7	XR_007079573.1	n.-128A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GEMIN6	ENST00000409011.5	c.-477T>C		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000387191.1
SRSF7	ENST00000446327.6	c.-366A>G		upstream_gene_variant		2		ENSP00000402264.2
SRSF7	ENST00000425778.5	n.-366A>G		upstream_gene_variant		2		ENSP00000400246.1

Frequencies

GnomAD3 genomes AF: 0.711 AC: 107705 AN: 151528 Hom.: 38474 Cov.: 29

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.780

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.731

GnomAD4 exome AF: 0.714 AC: 116159 AN: 162762 Hom.: 41956 Cov.: 0 AF XY: 0.715 AC XY: 62165 AN XY: 86914

African (AFR) AF: 0.726 AC: 4011 AN: 5524

American (AMR) AF: 0.671 AC: 6007 AN: 8950

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 3300 AN: 4248

East Asian (EAS) AF: 0.888 AC: 7416 AN: 8352

South Asian (SAS) AF: 0.732 AC: 19577 AN: 26742

European-Finnish (FIN) AF: 0.678 AC: 5193 AN: 7660

Middle Eastern (MID) AF: 0.770 AC: 471 AN: 612

European-Non Finnish (NFE) AF: 0.695 AC: 63937 AN: 92008

Other (OTH) AF: 0.721 AC: 6247 AN: 8666

GnomAD4 genome AF: 0.711 AC: 107768 AN: 151646 Hom.: 38491 Cov.: 29 AF XY: 0.713 AC XY: 52782 AN XY: 74070

African (AFR) AF: 0.715 AC: 29548 AN: 41332

American (AMR) AF: 0.695 AC: 10603 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 2708 AN: 3470

East Asian (EAS) AF: 0.881 AC: 4502 AN: 5110

South Asian (SAS) AF: 0.747 AC: 3582 AN: 4794

European-Finnish (FIN) AF: 0.665 AC: 6994 AN: 10514

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47326 AN: 67858

Other (OTH) AF: 0.734 AC: 1541 AN: 2100

Alfa AF: 0.695 Hom.: 4913

Bravo AF: 0.711

Asia WGS AF: 0.820 AC: 2850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.4
DANN	Benign	0.81
PhyloP100		-0.29
PromoterAI		0.071	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12621103; hg19: chr2-38978764;