NM_198546.1:c.812-48G>A

Variant names:

• chr1-16404087-C-T
• rs17419150
• NM_198546.1:c.812-48G>A

Variant summary

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

The NM_198546.1(SPATA21):​c.812-48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,351,976 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: SPATA21 NM_198546.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 13 publications found

Genes affected

SPATA21 (HGNC:28026): (spermatogenesis associated 21) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA21	NM_198546.1	c.812-48G>A		intron_variant	Intron 8 of 12	ENST00000335496.5	NP_940948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA21	ENST00000335496.5	c.812-48G>A		intron_variant	Intron 8 of 12	1	NM_198546.1	ENSP00000335612.1
SPATA21	ENST00000540400.1	c.743-48G>A		intron_variant	Intron 6 of 10	1		ENSP00000440046.1
SPATA21	ENST00000466212.5	n.2104-48G>A		intron_variant	Intron 10 of 16	2
SPATA21	ENST00000491418.5	c.-113G>A		upstream_gene_variant		5		ENSP00000420753.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1351976 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 669808

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

African (AFR) AF: 0.00 AC: 0 AN: 30508

American (AMR) AF: 0.00 AC: 0 AN: 35614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24902

East Asian (EAS) AF: 0.00 AC: 0 AN: 35504

South Asian (SAS) AF: 0.00 AC: 0 AN: 78228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4752

European-Non Finnish (NFE) AF: 0.00000193 AC: 2 AN: 1036948

Other (OTH) AF: 0.00 AC: 0 AN: 56288

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.65
PhyloP100		0.046
PromoterAI		0.012	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17419150; hg19: chr1-16730582;