rs535833314

Variant names:

• chr1-108877161-C-T
• rs535833314
• NM_013296.5:c.-316C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-108877161-C-T
• chr1-108877161-C-A
• chr1-108877161-C-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_013296.5(GPSM2):​c.-316C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 152,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GPSM2 NM_013296.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

Genes affected

GPSM2 (HGNC:29501): (G protein signaling modulator 2) The protein encoded by this gene belongs to a family of proteins that modulate activation of G proteins, which transduce extracellular signals received by cell surface receptors into integrated cellular responses. The N-terminal half of this protein contains 10 copies of leu-gly-asn (LGN) repeat, and the C-terminal half contains 4 GoLoco motifs, which are involved in guanine nucleotide exchange. This protein may play a role in neuroblast division and in the development of normal hearing. Mutations in this gene are associated with autosomal recessive nonsyndromic deafness (DFNB82). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

AKNAD1 (HGNC:28398): (AKNA domain containing 1) This gene encodes a protein which contains a domain found in an AT-hook-containing transcription factor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000309 (47/152216) while in subpopulation EAS AF = 0.00756 (39/5156). AF 95% confidence interval is 0.00569. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013296.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM2	NM_013296.5	MANE Select	c.-316C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_037428.3
	GPSM2	NM_013296.5	MANE Select	c.-316C>T		5_prime_UTR	Exon 1 of 15	NP_037428.3
	GPSM2	NM_001321038.2		c.-84C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_001307967.1	P81274

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPSM2	ENST00000264126.9	TSL:1 MANE Select	c.-316C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000264126.3	P81274
	GPSM2	ENST00000264126.9	TSL:1 MANE Select	c.-316C>T		5_prime_UTR	Exon 1 of 15	ENSP00000264126.3	P81274
	GPSM2	ENST00000674914.1		c.-127C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000501579.1	A0A6Q8PF02

Frequencies

GnomAD3 genomes AF: 0.000309 AC: 47 AN: 152102 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00754

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 60 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 56

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 54

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.000309 AC: 47 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 22 AN XY: 74422

African (AFR) AF: 0.00 AC: 0 AN: 41544

American (AMR) AF: 0.000523 AC: 8 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00756 AC: 39 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000329

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Chudley-McCullough syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.93
PhyloP100		-1.3
PromoterAI		-0.37	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs535833314; hg19: chr1-109419783;