6-85508320-TAAAAAAAA-TAAAAAAAAAA

Variant names:

• chr6-85508320-T-TAA
• rs765165360
• NM_153816.6:c.2654-263_2654-262dupTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_153816.6(SNX14):​c.2654-263_2654-262dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 868,110 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 0.0016 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00066 (0 hom.)
• Consequence: SNX14 NM_153816.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

Genes affected

SNX14 (HGNC:14977): (sorting nexin 14) This gene encodes a member of the sorting nexin family. Members of this family have a phox (PX) phosphoinositide binding domain and are involved in intracellular trafficking. The encoded protein also contains a regulator of G protein signaling (RGS) domain. Regulator of G protein signaling family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. Alternate splicing results in transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ENSG00000271793 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (159/98996) while in subpopulation AFR AF= 0.0057 (155/27194). AF 95% confidence interval is 0.00497. There are 1 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX14	NM_153816.6	c.2654-263_2654-262dupTT		intron_variant	Intron 26 of 28	ENST00000314673.8	NP_722523.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX14	ENST00000314673.8	c.2654-263_2654-262dupTT		intron_variant	Intron 26 of 28	1	NM_153816.6	ENSP00000313121.3
ENSG00000271793	ENST00000682083.1	n.*2564-263_*2564-262dupTT		intron_variant	Intron 37 of 39			ENSP00000506859.1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 159 AN: 99018 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00571

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000740

GnomAD4 exome AF: 0.000664 AC: 511 AN: 769114 Hom.: 0 Cov.: 0 AF XY: 0.000677 AC XY: 242 AN XY: 357362

Gnomad4 AFR exome AF: 0.00397

Gnomad4 AMR exome AF: 0.000816

Gnomad4 ASJ exome AF: 0.000968

Gnomad4 EAS exome AF: 0.000460

Gnomad4 SAS exome AF: 0.000656

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000599

Gnomad4 OTH exome AF: 0.000587

GnomAD4 genome AF: 0.00161 AC: 159 AN: 98996 Hom.: 1 Cov.: 31 AF XY: 0.00136 AC XY: 64 AN XY: 46982

Gnomad4 AFR AF: 0.00570

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs765165360; hg19: chr6-86218038;