NM_001396956.1:c.231C>T

Variant names:

• chr15-22460870-C-T
• rs527945774
• NM_001396956.1:c.231C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001396956.1(GOLGA6L22):​c.231C>T​(p.Ser77Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (2 hom., cov: 19)
  • Exomes 𝑓: 0.00027 (23 hom.)
  • Failed GnomAD Quality Control
• Consequence: GOLGA6L22 NM_001396956.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.784
• Publications: 0 publications found

Genes affected

GOLGA6L22 (HGNC:50289): (golgin A6 family like 22)

ENSG00000310081 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-22460870-C-T is Benign according to our data. Variant chr15-22460870-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644966.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.784 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396956.1. 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
	GOLGA6L22	NM_001396956.1	MANE Select	c.231C>T	p.Ser77Ser	synonymous	Exon 2 of 9	NP_001383885.1	H0YM25
	GOLGA6L22	NM_001396957.1		c.231C>T	p.Ser77Ser	synonymous	Exon 2 of 9	NP_001383886.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOLGA6L22	ENST00000622895.2	TSL:5 MANE Select	c.231C>T	p.Ser77Ser	synonymous	Exon 2 of 9	ENSP00000483673.2	H0YM25
	ENSG00000310081	ENST00000846990.1		n.152-7548G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000558 AC: 73 AN: 130910 Hom.: 2 Cov.: 19

Gnomad AFR AF: 0.000166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0117

Gnomad SAS AF: 0.000489

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000793

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000268 AC: 375 AN: 1397030 Hom.: 23 Cov.: 30 AF XY: 0.000253 AC XY: 176 AN XY: 694664

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000136 AC: 4 AN: 29518

American (AMR) AF: 0.0000237 AC: 1 AN: 42208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24158

East Asian (EAS) AF: 0.00743 AC: 292 AN: 39300

South Asian (SAS) AF: 0.000172 AC: 14 AN: 81498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3792

European-Non Finnish (NFE) AF: 0.0000337 AC: 36 AN: 1069706

Other (OTH) AF: 0.000488 AC: 28 AN: 57326

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000557 AC: 73 AN: 130976 Hom.: 2 Cov.: 19 AF XY: 0.000549 AC XY: 35 AN XY: 63810

African (AFR) AF: 0.000166 AC: 5 AN: 30104

American (AMR) AF: 0.000230 AC: 3 AN: 13062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3078

East Asian (EAS) AF: 0.0118 AC: 58 AN: 4936

South Asian (SAS) AF: 0.000489 AC: 2 AN: 4094

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 244

European-Non Finnish (NFE) AF: 0.0000793 AC: 5 AN: 63062

Other (OTH) AF: 0.00 AC: 0 AN: 1784

Alfa AF: 0.000164 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.6
DANN	Benign	0.32
PhyloP100		-0.78

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: rs527945774; hg19: chr15-22738231;