7-100463391-T-C

Variant names:

• chr7-100463391-T-C
• rs766139269
• NM_001004323.3:c.359A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001004323.3(SPACDR):​c.359A>G​(p.Gln120Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,252 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: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPACDR NM_001004323.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

SPACDR (HGNC:22135): (sperm acrosome developmental regulator) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TSC22D4-C7ORF61 (HGNC:):

TSC22D4 (HGNC:21696): (TSC22 domain family member 4) TSC22D4 is a member of the TSC22 domain family of leucine zipper transcriptional regulators (see TSC22D3; MIM 300506) (Kester et al., 1999 [PubMed 10488076]; Fiorenza et al., 2001 [PubMed 11707329]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33336073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPACDR	NM_001004323.3	c.359A>G	p.Gln120Arg	missense_variant	Exon 2 of 3	ENST00000332375.4	NP_001004323.1
TSC22D4-C7ORF61	NM_001395846.1	c.1274A>G	p.Gln425Arg	missense_variant	Exon 5 of 6		NP_001382775.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPACDR	ENST00000332375.4	c.359A>G	p.Gln120Arg	missense_variant	Exon 2 of 3	1	NM_001004323.3	ENSP00000327732.3
SPACDR	ENST00000418952.1	c.482A>G	p.Gln161Arg	missense_variant	Exon 1 of 2	2		ENSP00000412290.1
TSC22D4	ENST00000496728.1	n.805A>G		non_coding_transcript_exon_variant	Exon 5 of 5	3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000412 AC: 1 AN: 242742 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131934

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455252 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000389

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000826 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 11, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359A>G (p.Q120R) alteration is located in exon 2 (coding exon 2) of the C7orf61 gene. This alteration results from a A to G substitution at nucleotide position 359, causing the glutamine (Q) at amino acid position 120 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.5	L
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.44
MutPred		0.33		Loss of catalytic residue at Q120 (P = 0.0673);
MVP		0.27
MPC		0.49
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.39
gMVP		0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs766139269; hg19: chr7-100061014;