rs764166547

Variant names:

• chr21-42486396-T-A
• NM_080860.4:c.340A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-42486396-T-A
• chr21-42486396-T-C

Variant summary

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

The NM_080860.4(RSPH1):​c.340A>T​(p.Thr114Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RSPH1 NM_080860.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

Genes affected

RSPH1 (HGNC:12371): (radial spoke head component 1) This gene encodes a male meiotic metaphase chromosome-associated acidic protein. This gene is expressed in tissues with motile cilia or flagella, including the trachea, lungs, airway brushings, and testes. Mutations in this gene result in primary ciliary dyskinesia-24. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

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=0.30827004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPH1	NM_080860.4	c.340A>T	p.Thr114Ser	missense_variant	Exon 4 of 9	ENST00000291536.8	NP_543136.1
RSPH1	NM_001286506.2	c.226A>T	p.Thr76Ser	missense_variant	Exon 3 of 8		NP_001273435.1
RSPH1	XM_011529786.2	c.340A>T	p.Thr114Ser	missense_variant	Exon 4 of 8		XP_011528088.1
RSPH1	XM_005261208.3	c.133A>T	p.Thr45Ser	missense_variant	Exon 2 of 7		XP_005261265.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPH1	ENST00000291536.8	c.340A>T	p.Thr114Ser	missense_variant	Exon 4 of 9	1	NM_080860.4	ENSP00000291536.3
RSPH1	ENST00000398352.3	c.226A>T	p.Thr76Ser	missense_variant	Exon 3 of 8	5		ENSP00000381395.3
RSPH1	ENST00000493019.1	n.400A>T		non_coding_transcript_exon_variant	Exon 4 of 8	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461596 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.0093
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.16
Sift	Benign	0.28	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.48	P;.
Vest4		0.35
MutPred		0.37		Gain of glycosylation at T114 (P = 0.0357);.;
MVP		0.43
MPC		0.22
ClinPred		0.74	D
GERP RS		5.4
Varity_R		0.074
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-43906506;